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Distribution and morphology of non-persistent contrail and persistent contrail formation areas in ERA5
No full textThe contrail formation potential as well as its temporal and spatial distribution is estimated using me-
teorological conditions of temperature and relative humidity from the ERA5 re-analysis provided by the Euro-
pean Centre for Medium-Range Weather Forecasts. Contrail formation is estimated with the Schmidt–Appleman
criterion (SAc), solely considering thermodynamic effects. The focus is on a region ranging from the Eastern
United States (110–65° W) to central Europe (5° W–30° E). Around 18 000 flight trajectories from the In-service
Aircraft for a Global Observing System (IAGOS) are used as a representative subset of transatlantic, commercial
flights. The typical crossing distance through a contrail-prone area is determined based on IAGOS measurements
of temperature T and relative humidity r and then based on co-located ERA5 simulations of the same quantities.
Differences in spatial resolution between IAGOS and ERA5 are addressed from an aircraft-centered perspective,
using 1 km segments, and a model-centered perspective, using 19 km flight sections. Using the aircraft-centered
approach, 50 % of the crossings of persistent contrail (PC) regions based on IAGOS are shorter than 9 km, while
in ERA5 the median is 155 km. Time-averaged IAGOS data lead to a median crossing length of 66 km. The
difference between the two data sets is attributed to the higher variability of r in IAGOS compared to ERA5. The
model-centered approach yields similar results, but typical crossing lengths are larger by only up to 10 %. Binary
masks of PC formation are created by applying the SAc on the two-dimensional fields of T and r from ERA5.
In a second step the morphology of PC regions is also assessed. Half of the PC regions in ERA5 are found to
be smaller than ≈ 35 000 km2 (at 200 hPa), and the median of the maximum dimension is shorter than 760 km
(at 200 hPa). Furthermore, PC regions tend to be of near-circular shape with a tendency to a slight oval shape
and a preferred alignment along the dominant westerly flow. Seasonal, vertical distributions of PC formation
potential P are characterized by a maximum between 250 and 200 hPa. P is subject to seasonal variations with a
maximum in magnitude and extension during the winter months and a minimum during summer. The horizontal
distribution of PC regions suggests that PC regions are likely to appear in the same location on adjacent pressure
levels. Climatologies of T , r, wind speed U , and resulting PC formation potential are calculated to identify the
constraining effects of T and r on P. PC formation is primarily limited by conditions that are too warm below
and conditions that are too dry above the formation region. The distribution of PCs is slanted towards lower
altitudes from 30 to 70° N, following lines of constant T and r. For an observed co-location of high U and P,
it remains unclear whether PC formation and the jet stream are favored by the same meteorological conditions
or if the jet stream itself favors PC occurrence. This analysis suggests that some PC regions will be difficult to
avoid by rerouting aircraft because of their large vertical and horizontal extent
Enhanced reversal of ABCG2-mediated drug resistance by replacing a phenyl ring in baicalein with a meta-carborane
No full textSuccess of chemotherapy is often hampered by multidrug resistance. One mechanism for drug resistance is the elimination of anticancer drugs through drug transporters, such as breast cancer resistance protein (BCRP; also known as ABCG2), and causes a poor 5-year survival rate of human patients. Co-treatment of chemotherapeutics and natural compounds, such as baicalein, is used to prevent chemotherapeutic resistance but is limited by rapid metabolism. Boron-based clusters as meta-carborane are very promising phenyl mimetics to increase target affinity; we therefore investigated the replacement of a phenyl ring in baicalein by a meta-carborane to improve its affinity towards the human ABCG2 efflux transporter. Baicalein strongly inhibited the ABCG2-mediated efflux and caused a fivefold increase in mitoxantrone cytotoxicity. Whereas the baicalein derivative 5,6,7-trimethoxyflavone inhibited ABCG2 efflux activity in a concentration of 5 μm without reversing mitoxantrone resistance, its carborane analogue 5,6,7-trimethoxyborcalein significantly enhanced the inhibitory effects in nanomolar ranges (0.1 μm) and caused a stronger increase in mitoxantrone toxicity reaching similar values as Ko143, a potent ABCG2 inhibitor. Overall, in silico docking and in vitro studies demonstrated that the modification of baicalein with meta-carborane and three methoxy substituents leads to an enhanced reversal of ABCG2-mediated drug resistance. Thus, this seems to be a promising basis for the development of efficient ABCG2 inhibitors
Die neuzeitlichen Handschriften der Nullgruppe (Ms 0601-01200): Beschrieben von Detlef Döring
No full textDer dritte Band der Beschreibung der Leipziger neuzeitlichen Handschriften der Nullgruppe erfasst in erster Linie Texte zum Bereich der Wissenschafts und Universitätsgeschichte, wobei hier die Leipziger Hochschule einen Schwerpunkt bildet. Zu den Manuskripten gehören Vorlesungsnachschriften der verschiedensten wissenschaftlichen Disziplinen (17. bis 19. Jahrhundert), Korrespondenzen von Gelehrten, Werkmanuskripte, Tagebücher und archivalische Überlieferungen mehrerer wissenschaftlicher Organisationen (z.B. der germanistischen Sektion der Versammlung deutscher Philologen und Schulmänner). Eine erhebliche Anzahl von Handschriften betreffen verschiedene Orte und Territorien in der Zeit des Alten Reiches (z.B. Erzgebirge, Sachsen insgesamt, Elsass, Leipzig, Hildesheim). Außerhalb der thematisch zusammenfassbaren Handschriftengruppen stehen zahlreiche einzelne Bände, denen nicht selten ein hoher wissenschaftlicher Wert zukommt (z.B. eine Sammlung von Einblattdrucken des 16. Jahrhunderts, Aufzeichnungen zur französischen „Compagnie des Indes“, der Teilnachlass von Johann Friedrich Rochlitz zur Musikgeschichte)
Influence of Mutations and N-Glycosylation Sites in the Receptor-Binding Domain (RBD) and the Membrane Protein of SARS-CoV-2 Variants of Concern on Antibody Binding in ELISA
No full textSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect human cells by first attaching to the ACE-2 receptor via its receptor-binding domain (RBD) in the spike protein. Here, we report the influence of N-glycosylation sites of the RBD and the membrane (M) protein on IgG antibody binding in serum samples from patients infected with the original SARS-CoV-2 strain in Germany. The RBDs of the wildtype, alpha, beta, gamma, and kappa variants expressed in HEK293S GnTI− cells were all N-glycosylated at Asn331, Asn334, Asn343, and Asn360 or Asn370, whereas the M-protein was glycosylated at Asn5. An ELISA using a coated RBD and probed with anti-RBD IgG antibodies gave a sensitivity of 96.3% and a specificity of 100% for the wildtype RBD, while the sensitivity decreased by 5% to 10% for the variants of concern, essentially in the order of appearance. Deglycosylation of the wildtype RBD strongly reduced antibody recognition by ~20%, considering the mean of the absorbances recorded for the ELISA. This effect was even stronger for the unglycosylated RBD expressed in Escherichia coli, suggesting structural changes affecting epitope recognition. Interestingly, the N-glycosylated M-protein expressed in HEK293S GnTI− cells gave good sensitivity (95%), which also decreased to 65% after deglycosylation, and selectivity (100%). In conclusion, N-glycosylation of the M-protein, the RBD, and most likely the spike protein are important for proper antibody binding and immunological assays, whereas the type of N-glycosylation is less relevant
Oral Health-Related Quality of Life in Adult Patients with Depression or Attention Deficit Hyperactivity Disorder (ADHD)
No full textThe aim of this cross-sectional study was the evaluation of the oral health-related quality of
life (OHRQoL) in patients with depression or attention-deficit/hyperactivity disorder (ADHD) in
comparison with a group of mentally healthy individuals. Patients from the Department of Psychiatry
and Psychotherapy, University of Leipzig, Germany, were recruited. A healthy comparison group
(HC) was recruited from the Department of Cariology, Endodontology and Periodontology. The
OHRQoL was assessed using the Oral Health Impact Profile G14 (OHIP G14). Furthermore, a
questionnaire regarding oral hygiene behaviour was applied. A total of 141 patients with depression
or ADHD (depression n = 94, ADHD n = 47) and 145 HC individuals with a balanced age and
gender distribution were surveyed. OHIP G14 median scores were significantly higher in the overall
psychiatric patient group compared to HC (5.00 vs. 0.00, p < 0.001). This was also found for the four
dimensions of OHIP G14 (p < 0.001). The OHIP G14 sum score of patients with depression and ADHD
was comparable (5.00 vs. 6.50, p = 0.302). A significant association among psychiatric patients between
smoking, gum bleeding, professional tooth cleaning, oral health education, interdental cleaning, and
elevated OHIP scores was found (p < 0.001). In conclusion, patients with depression and adults with
ADHD show a reduced OHRQoL. A contradictory association between oral hygiene/oral health
behaviour and OHRQoL supports the hypothesis of a changed perception of oral conditions in
patients with mental diseases. Interdisciplinary collaboration between psychiatric specialists and
dentists should be fostered
Parent-perceived recurrent pain in children: associations with maternal pain, depressiveness, socioeconomic status, and children's behavioural difficulties
No full textThe current study aimed to examine the potential transgenerational
associations between maternal pain and depressiveness and childhood pain, and
to explore the associations between the children’s difficulties and recurrent pain
(defined as pain occurring at least once a month in the previous 6 month) in
healthy children aged 3–13 years
On the Optimization Properties of Optimal-Transport Based Generative Adversarial Linear Networks
No full textThis thesis is concerned with the analysis of the optimization problem in a class of generative models called Generative Adversarial Networks (GANs). GANs are successful generative models used to learn to mimic a given sampled distribution, and can be linked to Optimal Transport (OT) by the loss they rely on. OT is a reliable means to quantitatively compare two given probability distributions. The overall optimization problem is challenging as it involves a minimax optimization, in a generally highly non- convex-concave framework. In order to alleviate the analysis issues raised by this setting, several means can be employed. This thesis explores some of them in order to study a simplified OT-based generative model.
After introducing relevant mathematical tools in Chapter 2, we present in Chapter 3 the general framework of GANs, as well as the different simplifications that can be employed in order to derive analytical guarantees on the optimization system. Two examples, one discrete and one continuous, are investigated in order to illustrate how the analytical framework can be used in very simplified settings.
A particularly useful simplification is to reduce the minimax problem to a minimization problem only, by considering the maximization problem as being optimally solved at each time. In OT-based GAN, this typically boils down to analysing a type of distance between probability distributions, the Wasserstein distance. The minimization problem corresponds to finding a distribution that minimizes this distance to a given, target distribution. Chapters 4 and 5 leverage this simplification and study the landscape and convergence properties of a particular, linear OT-based GAN. In this case, the optimization problem can be cast as an overparametrized matrix factorization problem, combining a deep linear neural network with a covariance matrix parametrizations.
The landscape of the resulting loss, based on the so-called Bures-Wasserstein distance between the covariance matrices, is investigated in Chapter 4. More precisely, the critical points of the loss are derived, under the appropriate parametrizations. Given a rank constraint on the model covariance matrix, we make explicit the global minimizer to the matrix approximation problem. We find that they are are identical to the minimizers when considering a Euclidean distance between the covariance matrices. The Hessian of the loss at the critical points is derived and numerically investigated, in order to understand what differences the Euclidean and the Bures-Wasserstein distances may introduce in the optimization.
In Chapter 5, we analyze the gradient flow and gradient descent optimization schemes of this deep linear neural network under the Bures-Wasserstein loss. Convergence to minimizers of the loss is proven, under additional assumptions on the initialization of the scheme. The rank constraint on the approximation matrix appears here naturally as a bottleneck in the network representing the model covariance matrix.
Complementary to the main discussion about GANs, the thesis also includes a chapter on the optimization landscape in a supervised learning setting (Chapter 6 on mode connectivity). Its conclusions may be linked to the GAN discussion in the simplified, limited setting of a minimization-only optimization scheme
The AO Spine Thoracolumbar Injury Classification System and Treatment Algorithm in Decision Making for Thoracolumbar Burst Fractures Without Neurologic Deficit
No full textTo determine the alignment of the AO Spine Thoracolumbar Injury Classification system and treatment algorithm with contemporary surgical decision making
Study protocol for a feasibility study of microinterventions in smartphone-based assessments to reduce depressive rumination
No full textDepression as well as suicidal ideation and
behaviours share several precipitating and maintaining
factors and are subject to the influence of overlapping
constructs. One of these transdiagnostic constructs is
rumination. For the treatment of rumination, a variety of
interventions are already available. However, not everyone
with a need receives psychotherapeutic treatment. And
even if they do: implementing learnt strategies alone at
home can be challenging for patients. Therefore, this study
aims to test the feasibility of delivering microinterventions
for the reduction of rumination in a smartphone-based
setting with the goal to make these interventions
accessible to a larger number of people and support their
use in everyday life
The Role of Phosphatidylethanolamine N-Methyltransferase (PEMT) and ItsWaist-Hip-Ratio-Associated Locus rs4646404 in Obesity-Related Metabolic Traits and Liver Disease
No full textThis dissertation deals with the functional characterisation of the phosphatidylethanolamine N-methyltransferase (PEMT) gene and its single nucleotide polymorphism (SNP) rs4646404 in relation to the genesis of pathological fat distribution.
The scientific data for this work was collected in in vitro experiments on immortalised murine preadipocytes and through molecular biological studies on a human cohort.
In summary, a correlation between tissue-specific expression patterns of the gene in relation to visceral and subcutaneous adipose tissue was demonstrated. In addition, an association between tissue-specific gene expression and multiple metabolic parameters was identified in a human cohort.
The results were published in November 2023 in the 'International Journal of Molecular Sciences' (impact factor: 5.6 at the time of publication