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See detailUmstellung eines Campingplatzes auf solare Energieversorgung
Latz, Sebastian UL; Maas, Stefan UL

in Konferenzbeiträge Bauphysiktage Kaiserslautern 2022 (2022), 5

Der fortschreitende Klimawandel verlangt ein Umschwenken, weg von der fossilen Energieversorgung und hin zu den Erneuerbaren, wobei nachhaltige Tourismusangebote auch verstärkt einbezogen werden müssen ... [more ▼]

Der fortschreitende Klimawandel verlangt ein Umschwenken, weg von der fossilen Energieversorgung und hin zu den Erneuerbaren, wobei nachhaltige Tourismusangebote auch verstärkt einbezogen werden müssen. Der Campingplatz Treviris liegt auf dem Gelände des Rudervereins Treviris Trier und verzeichnet jährlich von Mitte April bis Mitte Oktober zwischen 40 und 50.000 Übernachtungen. Im Zuge des Neubaus des Bootshauses wird der vorhandene Gasanschluss zurückgebaut und die gesamte Wärme- und Stromversorgung der Liegenschaft muss auf regenerative Energien umgestellt werden. So soll der Bedarf des Campingplatzes, des Bootshauses (KfW 40 EE), der angegliederten Wohnbebauung mit zehn Wohneinheiten (KfW 40+) sowie mehrere Ladestationen emissionsneutral durch Sonnenenergie versorgt werden. Hauptbestandteile des Konzeptes sind eine 105 kWpeak PV Anlage mit 90 kWh Batteriespeicher sowie zwei Wärmepumpen, die um eine 80 m² hybride solarthermische Photovoltaikanlage (PVT) auf dem Campingplatz ergänzt werden soll. Insbesondere die Warmwasserversorgung des Campingplatzes ist hierbei eine Herausforderung, da die auftretenden Leistungsspitzen von 4m3 Warmwasser (WW) in 2 h nicht ausschließlich mittels Wärmepumpe bereitgestellt werden können. Es wird auf Wärmespeicher mit zentraler Frischwasserstation zurückgegriffen. Für die Dimensionierung der Hauptkomponenten: PVT Feld, Wärmepumpe und Pufferspeicher wird eine Zeitreihenanalyse mit variierendem Bedarf und schwankendem Solarangebot durchgeführt. [less ▲]

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See detailANALYSIS OF NEURODEVELOPMENTAL DEFECTS IN HUMAN MIDBRAIN ORGANOIDS FROM GBA-N370S PARKINSON'S DISEASE PATIENTS
Rosety, Isabel UL

Doctoral thesis (2022)

With increasing prevalence, Parkinson’s disease presents a major challenge for medical research and public health. Despite years of investigation, significant knowledge gaps exist and Parkinson’s disease ... [more ▼]

With increasing prevalence, Parkinson’s disease presents a major challenge for medical research and public health. Despite years of investigation, significant knowledge gaps exist and Parkinson’s disease (PD) etiology remains unclear. A recent concept in the field is that neurodevelopmental aspects might contribute to the pathogenesis of neurodegenerative diseases such as PD. Our hypothesis is that mutations in PD-linked genes have an impact on the cells’ homeostasis at the neural precursor state, giving rise to vulnerable dopaminergic (DA) neurons, thereby increasing the degree of susceptibility for neurodegeneration with aging. In order to investigate this, we used a human midbrain organoid (hMO) model generated from iPSC-derived neural precursor cells. As part of the optimization of the model, we treated the organoids with the neurotoxin 6-OHDA to develop a neurotoxin-induced PD model and set up a high-content imaging pipeline coupled with machine learning classification to predict neurotoxicity. We then used these tools to derive PD patient-derived hMOs in order to investigate our main hypothesis. First, we focused on PD patients carrying a heterozygous mutation in the GBA gene. We developed a genome-scale metabolic model that predicted significant differences in lipid metabolism between patients and controls. Then, we validated the observations by performing a comprehensive lipidomics analysis confirming a dysregulated lipidome in mutant hMOs. Moreover, GBA-PD hMOs displayed PD-relevant phenotypes, impaired DA differentiation and an increased population of neural progenitor cells (NPCs) in cell cycle arrest, confirming the presence of neurodevelopmental defects. To further investigate the neurodevelopmental component of PD, we used patient-derived cell lines carrying PINK1 mutations. PINK1-PD neural precursors presented differences in their energetic profile, imbalanced proliferation, apoptosis, mitophagy, and an impaired differentiation efficiency to DA neurons compared to controls. Correction of the PINK1 point mutation was able to improve the metabolic properties and neuronal firing rates as well as rescuing the differentiation phenotype. We performed a drug screen using repurposed drugs as well as novel compounds to evaluate their potential to rescue the observed developmental phenotype. Treatment with 2-hydroxypropyl-β- cyclodextrin increased the autophagy and mitophagy capacity of neurons which was accompanied by improved dopaminergic differentiation of patient-specific neurons in midbrain organoids and showed neuroprotective effects in an MPTP-treated mice PD model. In conlusion, PD has a neurodevelopmental component that increases susceptibility to the pathology. Thus, our findings suggest that the use of hMOs are suitable to reveal early PD pathomechanisms, as well as constituting a powerful tool for advanced therapy development. [less ▲]

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See detail"24.02.22, 5am: Testimonies from the War"
Scuto, Denis UL

Article for general public (2022)

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See detailBioremediation of 27 Micropollutants by Symbiotic Microorganisms of Wetland Macrophytes
Brunhoferova, Hana UL; Venditti, Silvia UL; Laczny, Cedric Christian UL et al

in Sustainability (2022), 14(7), 3944

Background: Micropollutants in bodies of water represent many challenges. We addressedthese challenges by the application of constructed wetlands, which represent advanced treatmenttechnology for the ... [more ▼]

Background: Micropollutants in bodies of water represent many challenges. We addressedthese challenges by the application of constructed wetlands, which represent advanced treatmenttechnology for the removal of micropollutants from water. However, which mechanisms specificallycontribute to the removal efficiency often remains unclear. Methods: Here, we focus on the removalof 27 micropollutants by bioremediation. For this, macrophytesPhragmites australis,Iris pseudacorusandLythrum salicariawere taken from established wetlands, and a special experimental set-up wasdesigned. In order to better understand the impact of the rhizosphere microbiome, we determinedthe microbial composition using 16S rRNA gene sequencing and investigated the role of identifiedgenera in the micropollutant removal of micropollutants. Moreover, we studied the colonizationof macrophyte roots by arbuscular mycorrhizal fungi, which are known for their symbiotic rela-tionship with plants. This symbiosis could result in increased removal of present micropollutants.Results: We foundIris pseudacorusto be the most successful bioremediative system, as it removed22 compounds, including persistent ones, with more than 80% efficiency. The most abundant generathat contributed to the removal of micropollutants werePseudomonas, Flavobacterium, Variovorax,Methylotenera, Reyranella, AmaricoccusandHydrogenophaga.Iris pseudacorusexhibited the highest colo-nization rate (56%). Conclusions: Our experiments demonstrate the positive impact of rhizospheremicroorganisms on the removal of micropollutants. [less ▲]

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See detailComments on Smithies
Raleigh, Thomas UL

in Asian Journal of Philosophy (2022), 1(13),

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See detailA posteriori error estimation for finite element approximations of fractional Laplacian problems and applications to poro–elasticity
Bulle, Raphaël UL

Doctoral thesis (2022)

This manuscript is concerned with a posteriori error estimation for the finite element discretization of standard and fractional partial differential equations as well as an application of fractional ... [more ▼]

This manuscript is concerned with a posteriori error estimation for the finite element discretization of standard and fractional partial differential equations as well as an application of fractional calculus to the modeling of the human meniscus by poro-elasticity equations. In the introduction, we give an overview of the literature of a posteriori error estimation in finite element methods and of adaptive refine- ment methods. We emphasize the state–of–the–art of the Bank–Weiser a posteriori error estimation method and of the adaptive refinement methods convergence results. Then, we move to fractional partial differential equations. We give some of the most common discretization methods of fractional Laplacian operator based equations. We review some results of a priori error estimation for the finite element discretization of these equations and give the state–of–the–art of a posteriori error estimation. Finally, we review the literature on the use of the Caputo’s fractional derivative in applications, focusing on anomalous diffusion and poro-elasticity applications. The rest of the manuscript is organized as follow. Chapter 1 is concerned with a proof of the reliability of the Bank–Weiser estimator for three–dimensional problems, extending a result from the literature. In Chapter 2 we present a numerical study of the Bank–Weiser estimator, provide a novel implementation of the estimator in the FEniCS finite element software and apply it to a variety of elliptic equations as well as goal-oriented error estimation. In Chapter 3 we derive a novel a posteriori estimator for the L2 error induced by the finite element discretization of fractional Laplacian operator based equations. In Chapter 4 we present new theoretical results on the convergence of a rational approximation method with consequences on the approximation of fractional norms as well as a priori error estimation results for the finite element discretization of fractional equations. Finally, in Chapter 5 we provide an application of fractional calculus to the study of the human meniscus via poro-elasticity equations. [less ▲]

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See detailThe History of Cross-Border Cooperation: some historiographical remarks
Brüll, Christoph UL

Scientific Conference (2022, March 24)

What is Cross-Border Cooperation? How to write the History of Cross-Border Cooperation? The contribution explores the historiography in the field and presents two case studies (Euregio Meuse-Rhine and ... [more ▼]

What is Cross-Border Cooperation? How to write the History of Cross-Border Cooperation? The contribution explores the historiography in the field and presents two case studies (Euregio Meuse-Rhine and Europäische Vereinigung Eifel-Ardennen). It focusses on the sources that could be used for such a history and on difficulties regarding archival research. [less ▲]

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See detailCNV-ClinViewer: Enhancing the clinical interpretation of large copy-number variants online
Macnee, Marie; Perez-Palma, Eduardo; Brünger, Tobias et al

E-print/Working paper (2022)

Purpose Large copy number variants (CNVs) can cause a heterogeneous spectrum of rare and severe disorders. However, most CNVs are benign and are part of natural variation in human genomes. CNV ... [more ▼]

Purpose Large copy number variants (CNVs) can cause a heterogeneous spectrum of rare and severe disorders. However, most CNVs are benign and are part of natural variation in human genomes. CNV pathogenicity classification, genotype-phenotype analyses, and therapeutic target identification are challenging and time-consuming tasks that require the integration and analysis of information from multiple scattered sources by experts. Methods We developed a web-application combining >250,000 patient and population CNVs together with a large set of biomedical annotations and provide tools for CNV classification based on ACMG/ClinGen guidelines and gene-set enrichment analyses. Results Here, we introduce the CNV-ClinViewer (https://cnv-ClinViewer.broadinstitute.org), an open-source web-application for clinical evaluation and visual exploration of CNVs. The application enables real-time interactive exploration of large CNV datasets in a user-friendly designed interface. Conclusion Overall, this resource facilitates semi-automated clinical CNV interpretation and genomic loci exploration and, in combination with clinical judgment, enables clinicians and researchers to formulate novel hypotheses and guide their decision-making process. Subsequently, the CNV-ClinViewer enhances for clinical investigators patient care and for basic scientists translational genomic research. [less ▲]

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See detailINCREASING THE COMPLEXITY OF MIDBRAIN ORGANOID SYSTEMS FOR DEVELOPMENTAL STUDIES AND DISEASE MODELLING
Sabaté Soler, Sonia UL

Doctoral thesis (2022)

The discovery of iPSC technology revolutionized the biomedical field, allowing the development of translatable and complex 2D and 3D cell culture systems. Organoids are 3D models containing multiple cell ... [more ▼]

The discovery of iPSC technology revolutionized the biomedical field, allowing the development of translatable and complex 2D and 3D cell culture systems. Organoids are 3D models containing multiple cell types that mimic complex microenvironments. This is highly advantageous to understand human development, physiology and disease, especially in inaccessible areas such as the brain. Human midbrain-specific organoids have been developed to study the midbrain (abundant in dopaminergic neurons). In Parkinson’s Disease (PD), dopaminergic neurons in the substantia nigra of the midbrain degenerate, causing a broad spectrum of clinical features. Midbrain organoids (MO) are rich in dopaminergic neurons, and contain spatially organized groups of neural cells and progenitors. MO generated from PD patients’ cells recapitulate dopaminergic neuron degeneration. In this thesis, we first demonstrated that dopaminergic neuron PD phenotypes and drug rescue effects were similar between MO and mice. After, we identified different neuronal clusters, progenitor cells, radial glia and mesenchymal cells in MO by scRNA-Seq. As expected, due to the neuro-ectodermal patterning of the MO’ starting cell population, we confirmed the absence of mesoderm-derived cell types, such as microglia and endothelial cells. This represents a limitation for the system in terms of cellular and molecular complexity. Microglia in the human brain perform surveillance, defence and homeostasis functions; they phagocytose metabolic waste products and cell debris. We successfully developed a novel protocol to integrate functional microglia into our MO model. SnRNA-Seq analysis and electrophysiological results suggested a reduction of stress levels and higher maturation of neurons in the presence of microglia, respectively. We then aimed to vascularise MO, which would better recapitulate the brain environment and improve oxygen and nutrient supply into the organoid core (a common 3D culture limitation). We integrated an endothelial network into MO by fusion with vascular organoids, and observed the presence of blood vessel components like pericytes and basal lamina. Furthermore, vascularized assembloids showed decreased levels of cell death and hypoxia. Finally, by co-culturing microglia with vascularized assembloids, we modelled the neurovascular unit in 3D. Altogether, this work contributes to the development of advanced 3D region-specific organoids, which better recapitulate the complexity of the human brain. These novel MO systems represent one step further into modelling neuroinflammation and blood brain barrier disruption, typical from neurodegenerative disorders such as PD, which might lead to more reliable and personalized medical approaches. [less ▲]

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See detailExplaining free will by rational capacities
Hofmann, Frank UL

in Ethical Theory and Moral Practice (2022)

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See detailPresentation in Computational Sciences PhD Presentation Day
Shang, Lan UL

Presentation (2022, March 22)

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See detailDigital twinning for enhancing breast cancer surgery
Mazier, Arnaud UL

Presentation (2022, March 22)

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See detailDevelopment of data integration tools within functional genomics
Teixeira Queiros, Pedro UL

Doctoral thesis (2022)

Due to technological advances across all scientific domains, data is generated at an extremely fast pace. This is especially true in biology, where advances in computational and sequencing technologies ... [more ▼]

Due to technological advances across all scientific domains, data is generated at an extremely fast pace. This is especially true in biology, where advances in computational and sequencing technologies led to the necessity to develop automated methods for data analysis; thus the field of bioinformatics was born. This thesis focuses on one specific field within bioinformatics - functional genomics. To be precise, in the development of techniques and software for the integration of data to generate novel insights. Indeed, as the amount of knowledge increases, so does the need to integrate it systematically. In this context, the work described herein relates to the integration of multiple resources to improve the functional annotation of proteins, which led to the development of two bioinformatic tools - Mantis and UniFunc. For the downstream integration and analysis of functional predictions, a network annotation tool was developed - UniFuncNet, which, together with the previous tools, enables the efficient functional characterisation of individual organisms or communities. [less ▲]

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See detailSpectrum of Phenotypic, Genetic, and Functional Characteristics in Epilepsy Patients With KCNC2 Pathogenic Variants 10.1212/WNL.0000000000200660
Schwarz, Niklas; Seiffert, Simone; Pendziwiat, Manuela et al

in Neurology (2022)

Background: KCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of ... [more ▼]

Background: KCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. The objective of this study was to analyse the clinical phenotype, genetic background, and biophysical function of disease-associated Kv3.2 variants.Methods: Individuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic, and functional analysis. Cases were referred through clinical and research collaborations. Selected de novo variants were examined electrophysiologically in Xenopus laevis oocytes.Results: We identified novel KCNC2 variants in 18 patients with various forms of epilepsy including genetic generalized epilepsy (GGE), developmental and epileptic encephalopathy (DEE) including early-onset absence epilepsy (EOAE), focal epilepsy (FE), and myoclonic-atonic epilepsy (MAE). 10/18 variants were de novo and 8/18 variants were classified as modifying variants. 8 drug responsive cases became seizure-free using valproic acid as monotherapy or in combination including severe DEE cases. Functional analysis of four variants demonstrated gain-of-function in three severely affected DEE cases and loss-of-function in one case with a milder phenotype (GGE) as the underlying pathomechanisms.Conclusion: These findings implicate KCNC2 as a novel causative gene for epilepsy and emphasize the critical role of KV3.2 in the regulation of brain excitability. [less ▲]

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See detailClosing Keynote: Networks, governance and design. A journey through some historical case studies
Schafer, Valerie UL

Presentation (2022, March 18)

As famous as the quotation by Lawrence Lessing “Code is law”, the sentence by David Clark at a meeting at the IETF in 1992 “We reject kings, presidents and voting, we believe in rough consensus and ... [more ▼]

As famous as the quotation by Lawrence Lessing “Code is law”, the sentence by David Clark at a meeting at the IETF in 1992 “We reject kings, presidents and voting, we believe in rough consensus and running code” became a “motto for Internet standardization” (Russell, 2006) that invites us to have a look at the past relationships and intertwinements between networks design and governance. From the 1970s topics related to distribution and openness have become key in networks infrastructures, while complementary issues related to asymmetries and multi-stakeholderism (Raymond and DeNardis 2015) have been emphasized in the 1990s and 2000s, and notably during the WSIS in Tunis and Geneva. Research related to Internet governance (Mueller and Badiei, 2020; Musiani, Schafer, 2021) has also brought to the table strong issues related to agencies, privacy, and many others that have strongly followed the development of networks and their uses as well as controversies related to net neutrality or information flows for example (DeNardis, 2020). This presentation will go through several historical case studies and rethink them through the lens of infrastructure design and governance, from Arpanet in the 1970s, XNS and then the OSI (Russell, 2014), to web archives (Schafer, Winters 2021) and research infrastructures today, through past designs and attempts, related to the Web and Xanadu, the Minitel (Schafer, Thierry, 2012; Mailland, Driscoll, 2017), platforms like Wuala (Musiani, 2022) and Wikipedia (Cardon and Levrel, 2009). This will allow us to explore some notions and approach related to closure, secret, incentives, empowerment, while finally moving from “governance” to “good governance” and its challenges. [less ▲]

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See detail"But you know you won't be back"
Scuto, Denis UL

Article for general public (2022)

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