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Heat recovery optimization of a shell and tube bundle heat exchanger with continuous helical baffles for air ventilation systems
We report a numerical evaluation of the impact of continuous helical baffle on the heat recovery efficiency of counterflow tube bundle heat exchangers. The baffle inclination angle has been varied from 11∘to 22∘. Since the fluid flows over the tube bundle at an angle due to helical flow inside the shell, the heat exchanger operates in cross counter mode. Fluent simulations with the k- ωtransition shear stress transport turbulence model have been performed to investigate the thermal-hydraulic parameters of the system in terms of heat recovery efficiency, pressure loss, and overall heat transfer rate. Outside air temperature has been varied to mimic cold and warm weather. Pressure loss has been constrained to be less than 250 Pa, conforming to EU guidelines for energy labeling of residential ventilation units. At the maximum volume flow rate of 40 m 3/h, the device performed with over 80%heat recovery efficiency for the considered temperature difference. Continuous helical baffles helped to improve convective heat transfer by reducing cross flow area and increasing velocity. Smaller angles result in greater pressure loss while having no discernible effect on heat recovery efficiency for the considered geometry. The analysis demonstrates the potential of a compact counterflowing recuperative heat exchanger with continuous helical baffles for decentralized ventilation systems and serves as a basis for further optimization.Open Access funding enabled and organized by Projekt DEAL.Zentrales Innovationsprogramm MittelstandFriedrich-Alexander-Universität Erlangen-Nürnberg (1041
Investigating Intravoxel Incoherent Motion Magnetic Resonance Imaging of the Liver and Kidney: Dependence on Acquisition Parameters and Techniques
Intravoxel incoherent motion (IVIM) is a concept in diffusion-weighted magnetic resonance imaging that enables the distinction between water diffusion and perfusion-related motion within biological tissues. There are still several mechanisms and influences of acquisition parameters that, to date, are not yet fully understood, which particularly limit the reproducibility and comparability of IVIM studies. This work placed a special focus on measurements in the liver and kidney. All measurements were supported and validated by in-silico investigations.
The first project aimed to investigate the influence of simultaneous multislice (SMS) acquisition, slice properties and repetition time (TR) on biexponential IVIM parameters in the liver. To investigate this research question, volunteer measurements were performed using conventional slice excitation (linear order) and SMS acquisition — both at a short TR (1,300 ms) and a long TR (4,500 ms) with 5 mm slice thickness. A subset of the volunteers was additionally measured with a thicker slice thickness of 10 mm at both short and long TR. The measurements, as expected, showed no difference in the biexponential IVIM parameters between linear slice order and SMS. Additionally, TR did not have an impact on the measured IVIM parameters in the 5 mm slices, but the influence on the perfusion fraction was more pronounced in the 10 mm thick slices. Simulations accounting for blood flow and T1 relaxation suggested that the perfusion fraction considerably depends on TR for slice settings with no slice gaps. Additionally, using an interleaved slice order instead of linear can influence the measured perfusion fraction for certain slice settings. Therefore, it is recommended to report slice thickness, size of slice gaps, and slice order in future IVIM publications.
The second project focused on the kidney to explore the contributions of blood and primary urine to the IVIM effect. To this end, the different T2 times of blood and primary urine were utilized, and images were acquired at four different echo times (TEs) (45 ms, 60 ms, 75 ms, and 90 ms). Biexponential IVIM parameters were then compared. Only the diffusion coefficient exhibited an increase at TE = 90 ms, while the perfusion fraction and the pseudodiffusion coefficeint remained constant across all TEs. Simulations using a multi-compartment model showed that the TE dependency of the perfusion fraction becomes virtually negligible when the volume fraction of primary urine does not exceed that of blood. They further show that, as the tubular fluid
volume increases, the TE dependence of the perfusion fraction becomes increasingly apparent. The sudden increase in the diffusion coefficient at TE = 90 ms might be either attributed to the presence of primary urine with small flow velocity, or it could be considered a mere artifact. In summary, the contribution of primary urine to the IVIM effect could neither be confirmed nor refuted so far. However, it was found that the biexponential IVIM parameters are
comparable across different TEs
Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients
Biallelic loss of SPG11 function constitutes the most frequent cause of complicated autosomal recessive hereditary spastic paraplegia (HSP) with thin corpus callosum, resulting in progressive multisystem neurodegeneration. While the impact of neuroinflammation is an emerging and potentially treatable aspect in neurodegenerative diseases and leukodystrophies, the role of immune cells in SPG11–HSP patients is unknown. Here, we performed a comprehensive immunological characterization of SPG11–HSP, including examination of three human postmortem brain donations, immunophenotyping of patients’ peripheral blood cells and patient-specific induced pluripotent stem cell-derived microglia-like cells (iMGL). We delineate a previously unknown role of innate immunity in SPG11–HSP. Neuropathological analysis of SPG11–HSP patient brain tissue revealed profound microgliosis in areas of neurodegeneration, downregulation of homeostatic microglial markers and cell-intrinsic accumulation of lipids and lipofuscin in IBA1 + cells. In a larger cohort of SPG11–HSP patients, the ratio of peripheral classical and intermediate monocytes was increased, along with increased serum levels of IL-6 that correlated with disease severity. Stimulation of patient-specific iMGLs with IFNγ led to increased phagocytic activity compared to control iMGL as well as increased upregulation and release of proinflammatory cytokines and chemokines, such as CXCL10. On a molecular basis, we identified increased STAT1 phosphorylation as mechanism connecting IFNγ-mediated immune hyperactivation and SPG11 loss of function. STAT1 expression was increased both in human postmortem brain tissue and in an Spg11 –/– mouse model. Application of an STAT1 inhibitor decreased CXCL10 production in SPG11 iMGL and rescued their toxic effect on SPG11 neurons. Our data establish neuroinflammation as a novel disease mechanism in SPG11–HSP patients and constitute the first description of myeloid cell/ microglia activation in human SPG11–HSP. IFNγ/ STAT1-mediated neurotoxic effects of hyperreactive microglia upon SPG11 loss of function indicate that immunomodulation strategies may slow down disease progression.Open Access funding enabled and organized by Projekt DEAL.Bundesministerium für Bildung und Forschunghttp://dx.doi.org/10.13039/501100002347Förderverein für HSP ForschungDeutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659Bayerisches Staatsministerium für Bildung und Kultus, Wissenschaft und Kunsthttp://dx.doi.org/10.13039/501100004563Research Foundation Medicine at the University Clinic ErlangenTom Wahlig FoundationEU Horizon 2020 programSenior Clinical Researcher mandate of the Research Fund - Flanders (FWO)European Reference Network for Rare Neuromuscular Diseases (ERN EURO-NMD)European Reference Network for Rare Neurological Diseases (ERN-RND)µNEURO Research Centre of Excellence of the University of AntwerpFriedrich-Alexander-Universität Erlangen-Nürnberg (1041
MCMC sampling of directed flag complexes with fixed undirected graphs
Constructing null models to test the significance of extracted information is a crucial step in data analysis. In this work, we provide a uniformly sampleable null model of directed graphs with the same (or similar) number of simplices in the flag complex, with the restriction of retaining the underlying undirected graph. We describe an MCMC-based algorithm to sample from this null model and statistically investigate the mixing behaviour. This is paired with a high-performance, Rust-based, publicly available implementation. The motivation comes from topological data analysis of connectomes in neuroscience. In particular, we answer the fundamental question: are the high Betti numbers observed in the investigated graphs evidence of an interesting topology, or are they merely a byproduct of the high numbers of simplices? Indeed, by applying our new tool on the connectome of C. elegans and parts of the statistical reconstructions of the Blue Brain Project, we find that the Betti numbers observed are considerable statistical outliers with respect to this new null model. We thus, for the first time, statistically confirm that topological data analysis in microscale connectome research is extracting statistically meaningful information.Open access funding provided by Graz University of Technology.Graz University of Technolog
In Vivo Assessment of Deep Vascular Patterns in Murine Colitis Using Optoacoustic Mesoscopic Imaging
The analysis of vascular morphology and functionality enables the assessment of disease activity and therapeutic effects in various pathologies. Raster‐scanning optoacoustic mesoscopy (RSOM) is an imaging modality that enables the visualization of superficial vascular networks in vivo. In murine models of colitis, deep vascular networks in the colon wall can be visualized by transrectal absorber guide raster‐scanning optoacoustic mesoscopy (TAG‐RSOM). In order to accelerate the implementation of this technology in translational studies of inflammatory bowel disease, an image‐processing pipeline for TAG‐RSOM data has been developed. Using optoacoustic data from a murine model of chemically‐induced colitis, different image segmentation methods are compared for visualization and quantification of deep vascular patterns in terms of vascular network length and complexity, blood volume, and vessel diameter. The presented image‐processing pipeline for TAG‐RSOM enables label‐free in vivo assessment of changes in the vascular network in murine colitis with broad applications for inflammatory bowel disease research.Transrectal absorber guide raster‐scanning optoacoustic mesoscopy (TAG‐RSOM) enables transabdominal in vivo imaging of murine colitis. For advanced visualization and quantification of deep vascular patterns different image segmentation methods are applied. The presented image‐processing pipeline for TAG‐RSOM enables label‐free in vivo assessment of changes in the vascular network in murine colitis with broad applications for inflammatory bowel disease research. imageElse Kröner‐Fresenius‐Stiftung http://dx.doi.org/10.13039/501100003042Cancer Research UK http://dx.doi.org/10.13039/50110000028
Guidelines for Neuroprognostication in Critically Ill Adults with Moderate–Severe Traumatic Brain Injury
Background Moderate–severe traumatic brain injury (msTBI) carries high morbidity and mortality worldwide. Accurate neuroprognostication is essential in guiding clinical decisions, including patient triage and transition to comfort measures. Here we provide recommendations regarding the reliability of major clinical predictors and prediction models commonly used in msTBI neuroprognostication, guiding clinicians in counseling surrogate decision-makers. Methods Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, we conducted a systematic narrative review of the most clinically relevant predictors and prediction models cited in the literature. The review involved framing specific population/intervention/comparator/outcome/timing/setting (PICOTS) questions and employing stringent full-text screening criteria to examine the literature, focusing on four GRADE criteria: quality of evidence, desirability of outcomes, values and preferences, and resource use. Moreover, good practice recommendations addressing the key principles of neuroprognostication were drafted. Results After screening 8125 articles, 41 met our eligibility criteria. Ten clinical variables and nine grading scales were selected. Many articles varied in defining “poor” functional outcomes. For consistency, we treated “poor” as “unfavorable”. Although many clinical variables are associated with poor outcome in msTBI, only the presence of bilateral pupillary nonreactivity on admission, conditional on accurate assessment without confounding from medications or injuries, was deemed moderately reliable for counseling surrogates regarding 6-month functional outcomes or in-hospital mortality. In terms of prediction models, the Corticosteroid Randomization After Significant Head Injury (CRASH)-basic, CRASH-CT (CRASH-basic extended by computed tomography features), International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-core, IMPACT-extended, and IMPACT-lab models were recommended as moderately reliable in predicting 14-day to 6-month mortality and functional outcomes at 6 months and beyond. When using “moderately reliable” predictors or prediction models, the clinician must acknowledge “substantial” uncertainty in the prognosis. Conclusions These guidelines provide recommendations to clinicians on the formal reliability of individual predictors and prediction models of poor outcome when counseling surrogates of patients with msTBI and suggest broad principles of neuroprognostication
Der Einfluss des spannungsabhängigen L-Typ-Calciumkanal-Antagonisten Nimodipin auf die Entwicklung von Oligodendrozyten-Vorläuferzellen
Gliazellen wie Oligodendrozyten und Astrozyten spielen unverzichtbare Rollen im zentralen Ner-vensystem, die für dessen ordnungsgemäße Funktion entscheidend sind. Oligodendrozyten unter-stützen durch die Bildung von Myelin die Reizweiterleitung durch elektrische Isolation und bieten gleichzeitig Schutz für die Axone. Krankheiten wie die Multiple Sklerose können zu Demyelinisie-rung führen, was wiederum zum Verlust von Axonen und zur Neurodegeneration beiträgt. Ein Hauptforschungsziel ist daher die Untersuchung von Mechanismen zur Remyelinisierung. Eine vielversprechende, jedoch bisher wenig erforschte Möglichkeit zur Initiierung der Remyelinisierung sind Calciumsignalprozesse im zentralen Nervensystem. Es ist bekannt, dass spannungsabhängige Calciumkanäle die Differenzierung und Myelinisierung von Oligodendrozyten-Vorläuferzellen be-einflussen. Nimodipin, ein Antagonist von L-Typ-Calciumkanälen, wird schon länger als vielver-sprechende Option für die Behandlung von demyelinisierenden Erkrankungen betrachtet. Diese Dissertation untersucht den Effekt von Nimodipin auf Oligodendrozyten-Vorläuferzellen und reife Oligodendrozyten sowohl in vitro als auch in vivo.
Zunächst wurden Co-Kultur-Systeme bestehend aus Oligodendrozyten und Neuronen mit Nimo-dipin behandelt, wobei eine erhöhte Anzahl von Oligodendrozyten festgestellt wurde. Um den isolierten Effekt von Nimodipin auf Oligodendrozyten-Vorläuferzellen und reife Oligodendrozy-ten weiter zu untersuchen, wurden die Oligodendrozyten-Vorläuferzelllinie Oli-Neu, primäre murine Oligodendrozyten-Vorläuferzellen und die humane reife Oligodendrozytenzelllinie MO3.13 mittels PCR, Immunzytochemie und Patch-Clamp-Technik charakterisiert. Die Zelllinie Oli-Neu und die primär isolierten murinen Oligodendrozyten-Vorläuferzellen zeigten in vitro cha-rakteristische und ähnliche Eigenschaften von Oligodendrozyten-Vorläuferzellen, die humane Oli-godendrozytenzelllinie MO3.13 zeigte in vitro Charakteristika von reifen Oligodendrozyten. Zum einen führte die Behandlung von Oli-Neu-Zellen und Primärzellen mit Nimodipin nicht zu einer erhöhten Expression von Myelingenen und -proteinen, obwohl Nimodipin physiologisch aktiv und eine Bindung an spannungsabhängige Calciumkanäle nachweisbar war. Zum anderen zeigten elekt-ronenmikroskopische Untersuchungen der Ultrastruktur der Zellen jedoch eine gesteigerte Anzahl lipophiler Körper in Oli-Neu-Zellen nach Behandlung mit Nimodipin, die sich anhand von Im-munogold-Färbungen als positiv für das basische Myelinprotein (MBP) erwiesen. RNA-Sequenzie-rung von Oli-Neu-Zellen nach Nimodipin-Behandlung deutete darüber hinaus darauf hin, dass Nimodipin die Expression von miRNAs beeinflussen kann, die für die Myelinisierung relevant sein könnten. Validierungsexperimente, die sich der Technik der qPCR bedienten, konnten allerdings keinen Einfluss von Nimodipin auf die Expression der bei der Sequenzierung identifizierten Top-miRNA-Hits zeigen, weder in Oli-Neu-Zellen noch in den zusätzlich getesteten MO3.13-Zellen. Weitere Untersuchungen zum Einfluss von Nimodipin auf die Migration von MO3.13-Zellen zeig-ten ebenfalls keinen Effekt. Zum Abschluss wurden mögliche In-vivo-Effekte von Nimodipin mit-tels des Zebrafischmodells untersucht. Hier deuteten die Ergebnisse darauf hin, dass Nimodipin die Auswanderung reifer Oligodendrozyten aus dem Neuralrohr verstärkte.
Zusammenfassend betrachtet unterscheiden sich die in vitro von den in vivo beobachteten Effekten von Nimodipin auf reife Oligodendrozyten und deren Vorläuferzellen. Allerdings bleibt der genaue Wirkmechanismus von Nimodipin unklar. Die Klärung der möglichen Mechanismen kann Ziel zukünftiger Studien sein. Darüber hinaus können klinische Studien Aufschluss geben, ob Nimodi-pin als ein potenzielles Medikament zur Behandlung von demyelinisierenden Erkrankungen wie der Multiplen Sklerose nutzbar sein kann
High-Intensity Laser-Target Interactions for Applications in Laboratory Astrophysics
Over the past decades, there has been a significant effort to study the interactions of high-intensity, short-pulse lasers with solid-density targets due to their numerous crossfield applications. Understanding the plasma phenomena taking place during the formation of these extreme states of matter in the laboratory ultimately will lead to significant advances in a plethora of fields, including laser-plasma driven particle accelerators, translational research for radiation oncology, laboratory astrophysics, inertial confinement fusion, and material degradation studies for future fission and fusion reactors. However, the microphysics of many relativistic laser-plasma processes, such as plasma heating, field generation, and shock formation, are still not understood.
In particular, the role of kinetic plasma instabilities, such as the Weibel or current filamentation instability, in fundamental plasma processes, such as electron transport, magnetic field amplification, and ion acceleration, remains an open question. In astrophysical environments, these instabilities are thought to govern the seeding and amplification of magnetic fields, leading to the formation of collisionless shocks, which are capable of accelerating particles to extreme energies and thus form large parts of the cosmic ray spectrum that is measured on Earth. The formation of these collisionless shocks, however, is still a highly debated topic, to which laboratory experiments can offer particularly valuable insights into the involved instabilities. Yet, the direct experimental observation and detailed characterization of the current filamentation instability in solid density plasmas has been challenged due to the limitations of conventional diagnostics to probe the high plasma density with great precision.
This thesis presents the results of an experiment conducted at the SLAC National Accelerator Laboratory Linac Coherent Light Source X-ray laser, during which the solid density region of the relativistic laser-plasma interaction was successfully imaged for the first time. The images show the development and growth of density filaments associated with the current filamentation instability and suggest the importance of ion motion in facilitating the instability growth. The filament structures are analyzed through a standardized method developed specifically for this thesis, which enables the extraction of the filament wavelength and integrated filament density.
These observations are used to benchmark fully kinetic PIC simulations and analytical models, revealing details of a more intricate process of this instability growing in an asymmetric regime. Furthermore, at later times the hydrodynamic evolution of the high-intensity laser-solid interaction is revealed, featuring a laser-generated shock wave moving at an average velocity of 80 km/s. The preliminary analysis of these shocks is compared with basic magnetohydrodynamic models and shows the results to be consistent with a rarefaction wave attenuating an initially strong shock wave generated during the high-intensity shortpulse
laser interaction. Finally, a cryogenic liquid jet target system is discussed as a key element for the ongoing effort to extend High Energy Density science experiments, such as the one described in this thesis, to high-repetition rate. As such, this thesis lays the foundation of the direct experimental observation and characterization of plasma instabilities at solid density and provides a guide for future studies of relativistic laser-solid interactions
Postmortal epithelial changes of donor corneas impair applicability of a refractive ultraviolet femtosecond laser
This study evaluates the corneal applicability of a refractive ultraviolet femtosecond laser in postmortal human donor eyes and ex vivo porcine eyes. Refractive lenticule extraction and flap creation were attempted in 10 human donor eyes and 80 ex vivo porcine eyes with and without abrasion of the corneal epithelium. The postmortem interval ranged from 6 to 35 h in the human samples and was set to 4, 24, and 48 h for the porcine specimens. Nine human eyes and 60 porcine eyes were treated with an ultraviolet femtosecond laser. The rest was treated with an infrared laser. Optical coherence tomography and scanning electron microscopy were used to demonstrate success or failure of the procedures. Ultraviolet laser-assisted refractive surgery attempts without prior abrasion of the corneal epithelium were only successful at 6 h p.m. in the human eyes and at 4 and 24 h in the porcine eyes. Upon epithelial abrasion, refractive surgery was always successful with the ultraviolet laser. The infrared laser always performed successfully with and without prior epithelial abrasion. Thus, postmortal changes in the corneal epithelium impair the ability of refractive ultraviolet femtosecond lasers to create stromal cuts. This progresses with time but does not affect infrared femtosecond lasers.Open Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041