Funktionale Klassifizierung von Kleinstädten in Deutschland: Ein methodischer Vergleich

Die Entwicklung von deutschen Kleinstädten hinsichtlich ihrer ökonomischen, demographischen und sozialen Ausstattung ist ein bislang eher unbeachteter Themenbereich. Es werden oftmals Kleinstädte in ländlichen und peripheren Lagen thematisiert, weil man ihnen ausschließlich hier eine gewisse Rolle zuweist. Kleinstädte in zentralen Lagen hingegen werden in der Forschung unter dem suburbanen Raum subsumiert und damit selten hinsichtlich ihrer spezifischen Funktionen betrachtet. In diesem Beitrag werden alle Kleinstädte in Deutschland hinsichtlich wichtiger Funktionen klassifiziert. Die Typisierung erfolgt mittels einer Clusteranalyse, die auf zentralen Faktoren basiert, welche sich auf ein breites Indikatorenset stützen. Bezugspunkte sind dabei das klassische Verfahren der Hauptkomponentenanalyse sowie als Alternativmethode die geographisch gewichtete Hauptkomponentenanalyse. Im methodischen Vergleich zeigt sich, dass die Alternative - auch aufgrund des hohen Rechenaufwands - noch keine geeignete Methode ist, um räumliche Zusammenhänge zwischen den Variablen abzubilden und die Kleinstädte hinsichtlich bestehender funktionaler Ausstattungen in ihrem Umland besser beschreiben zu können. Hingegen erzeugt die in der Literatur vorzufindende Vorgehensweise aus Hauptkomponentenanalyse, Clusteranalyse und Diskriminanzanalyse gut abgrenzbare und erklärbare Lösungen zur Bildung von Kleinstadttypen in Deutschland.The development of small towns in Germany in terms of their economic, demographic and social endowment is a subject area that has been rather neglected so far. What is more, research often focuses exclusively on small towns in rural and peripheral regions, because this is the only place where they are assigned a certain role. Small towns in central areas, on the other hand, are subsumed under suburbia in research and are thus rarely considered in terms of their specific functions. In this paper, all small towns in Germany are classified with regard to important functions. The typification is done by means of a cluster analysis based on central factors, which in turn are tied to a broad set of indicators. Reference points are the classical method of principal component analysis and, as an alternative method, to geographically weighted principal component analysis. The methodological comparison shows that the alternative method - also due to the high computational effort - is not yet a suitable method for describing spatial relationships between the variables and for small towns with regard to existing functions in their surrounding areas. On the other hand, the approach of the principal component analysis, cluster analysis and discriminant analysis, which is found in the literature, produces well defined and explainable solutions for the formation of different types of small towns in Germany

Coupled soil-structure interaction modeling and simulation of landslide protective structures

Within the past two decades, mass movements hazards involving fast and large soil deformation have increased significantly in frequency and magnitude due to their strong relation to climate changes and global warming. These phenomena often bring along rocks, debris, and heavy materials that can extensively damage and destroy the landscape and infrastructures, causing devastating economic loss, and often, human casualties. The risk of future disasters continues to escalate with the increase of real estate development in suburban areas, including mountainous regions. Further assessment and prediction on such disasters and their countermeasures are, therefore, in high economic demands. One of the most intuitive ways is to install protective structures in mountain slopes and valleys that can hold the materials brought by the moving landslides. While the current state of the art of landslide prediction using numerical methods has been mainly dominated by the development of advanced geomechanical models suited for different types of soil materials, e.g. multi-phase unsaturated soil model, this study focuses more on the interaction of such phenomena with the installed protective structures. Here, an implicit formulation of material point method (MPM) is implemented to model the landslides considering finite strain assumption. Furthermore, a staggered coupling scheme with traditional Finite Element Method (FEM) is proposed to simulate accurately and robustly the dynamic force and displacement coupling of soil-structure interaction (SSI). All developments of the method are implemented within the Kratos-Multiphysics framework [1] and available under the BSD license (https://github.com/KratosMultiphysics/Kratos/wiki). In the future works, more adequate consideration of coupling scheme and material models considering damage and fracture will be investigated before conducting a real-scale landslide simulation

Fulminant Cardiotoxicity in a Patient With Cardiac Lymphoma Treated With CAR-T Cells

[Figure: see text

β6-Integrin Serves as a Potential Serum Marker for Diagnosis and Prognosis of Pancreatic Adenocarcinoma

INTRODUCTION Despite enormous efforts during the past decades, pancreatic adenocarcinoma (PAC) remains one of the most deleterious cancer entities. A useful biomarker for early detection or prognosis of PAC does not yet exist. The goal of our study was the characterization of β6-integrin (ITGB6) as a novel serum tumor marker for refined diagnosis and prognosis of PAC. Serum ITGB6 levels were analyzed in 3 independent PAC cohorts consisting of retrospectively and prospectively collected serum and/or (metastatic) PAC tissue specimens. METHODS Using 2 independent cohorts, we measured serum ITGB6 concentrations in 10 chronic pancreatitis patients, 10 controls, as well as in 27 (cohort 1) and 24 (cohort 2) patients with PAC, respectively. In these patients, we investigated whether ITGB6 serum levels correlate with known clinical and prognostic markers for PAC and whether they might differ between patients with PAC or benign inflammatory diseases of the pancreas. RESULTS We found that elevated serum ITGB6 levels (≥0.100 ng/mL) in patients suffering from metastasizing PAC presented an unfavorable prognostic outcome. By correlating the ITGB6 tissue expression in primary and metastatic PAC with clinical parameters, we found that positive ITGB6 expression in the tumor tissue is linked to increased serum ITGB6 levels in nonmetastatic PAC and correlates with carbohydrate antigen 19-9 and clinical outcome. DISCUSSION Our findings suggest that ITGB6 might serve as a novel serum biomarker for early diagnosis and prognosis of PAC. Given the limited specificity and sensitivity of currently used carbohydrate antigen 19-9-based assays, ITGB6 may have the potential to improve the diagnostic accuracy for PAC

On the electronic impact of abnormal C4-bonding in N-heterocyclic carbene complexes

Sterically similar palladium dicarbene complexes have been synthesized that comprise permethylated dicarbene ligands which bind the metal center either in a normal coordination mode via C2 or abnormally via C4. Due to the strong structural analogy of the complexes, differences in reactivity patterns may be attributed to the distinct electronic impact of normal versus abnormal carbene bonding, while stereoelectronic effects are negligible. Unique reactivity patterns have been identified for the abnormal carbene complexes, specifically upon reaction with Lewis acids and in oxidative addition-reductive elimination sequences. These reactivities as well as analytical investigations using X-ray diffraction and X-ray photoelectron spectroscopy indicate that the C4 bonding mode increases the electron density at the metal center substantially, classifying such C4-bound carbene ligands amongst the most basic neutral donors known thus far. A direct application of this enhanced electron density at the metal center is demonstrated by the catalytic H₂ activation with abnormal carbene complexes under mild conditions, leading to a catalytic process for the hydrogenation of olefins

A Novel NHE1-Centered Signaling Cassette Drives Epidermal Growth Factor Receptor–Dependent Pancreatic Tumor Metastasis and Is a Target for Combination Therapy

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers principally because of early invasion and metastasis. The epidermal growth factor receptor (EGFR) is essential for PDAC development even in the presence of Kras, but its inhibition with erlotinib gives only a modest clinical response, making the discovery of novel EGFR targets of critical interest. Here, we revealed by mining a human pancreatic gene expression database that the metastasis promoter Na+/H+ exchanger (NHE1) associates with the EGFR in PDAC. In human PDAC cell lines, we confirmed that NHE1 drives both basal and EGF-stimulated three-dimensional growth and early invasion via invadopodial extracellular matrix digestion. EGF promoted the complexing of EGFR with NHE1 via the scaffolding protein Na +/H + exchanger regulatory factor 1, engaging EGFR in a negative transregulatory loop that controls the extent and duration of EGFR oncogenic signaling and stimulates NHE1. The specificity of NHE1 for growth or invasion depends on the segregation of the transient EGFR/Na +/H + exchanger regulatory factor 1/NHE1 signaling complex into dimeric subcomplexes in different lipid raftlike membrane domains. This signaling complex was also found in tumors developed in orthotopic mice. Importantly, the specific NHE1 inhibitor cariporide reduced both three-dimensional growth and invasion independently of PDAC subtype and synergistically sensitized these behaviors to low doses of erlotinib

SCD5 Regulation by VHL Affects Cell Proliferation and Lipid Homeostasis in ccRCC

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cancer, and inactivation of the VHL tumor suppressor gene is found in almost all cases of hereditary and sporadic ccRCCs. CcRCC is associated with the reprogramming of fatty acid metabolism, and stearoyl-CoA desaturases (SCDs) are the main enzymes controlling fatty acid composition in cells. In this study, we report that mRNA and protein expression of the stearoyl-CoA desaturase SCD5 is downregulated in VHL-deficient cell lines. Similarly, in C. elegans vhl-1 mutants, FAT-7/SCD5 activity is repressed, supporting an evolutionary conservation. SCD5 regulation by VHL depends on HIF, and loss of SCD5 promotes cell proliferation and a metabolic shift towards ceramide production. In summary, we identify a novel regulatory function of VHL in relation to SCD5 and fatty acid metabolism, and propose a new mechanism of how loss of VHL may contribute to ccRCC tumor formation and progression

Workshop on PIDs within NFDI: Report of the Working Group “Persistent Identifiers (PID)” of the Section Common Infrastructures of the NFDI

In order to gain an overview of the current state of the discussion on PIDs and for the identification of use cases for the initiation phase of a PID service within the NFDI basic services, the working group Persistent Identifier of the Section Common Infrastructures of the NFDI hosted an online workshop in January 2023. In the course of the workshop, members of nine different NFDI consortia presented the current application of PIDs in their consortia