Nonrenal regulation of EPO synthesis

Erythropoietin (EPO) is a circulating glycoprotein hormone whose principal function is thought to be red blood cell production. It is a classic example of a hypoxia-inducible gene, and studies of the induction of EPO synthesis by low oxygen led to the discovery of a widespread system of hypoxia-inducible transcription factors. Tissue-specific expression of the EPO gene is tightly controlled, and in the adult organism the kidney produces around 90% of systemic EPO. Before birth, the liver is the main site of EPO production; factors contributing to the liver-to-kidney switch are still elusive, but may provide clues to the tissue-specificity of EPO gene expression. EPO has also been detected in non-erythropoietic tissues such as the brain, where it is suggested to exert local protective effects. Apart from classical ways of regulating renal EPO during hypoxia and anemia, novel pathways have been discovered that demonstrate that other organ systems in the adult might not only be important for the production of EPO but also for modulating the hypoxic EPO response. Knowledge of the molecular bases of these non-renal pathways will eventually help to develop pharmacological strategies to induce endogenous EPO production when the main source, the kidney, is significantly impaired. This review will provide an overview of the molecular aspects of EPO gene regulation by hypoxia-inducible transcription factors and of the tissue-specific regulation of EPO production in adult mammals. Insights into the biology of EPO production in genetically modified animals, with an emphasis on recent advances in the understanding of non-renal EPO regulation, will be discussed

Low Luminosity Companions to White Dwarfs

This paper presents results of a near-infrared imaging survey for low mass stellar and substellar companions to white dwarfs. A wide field proper motion survey of 261 white dwarfs was capable of directly detecting companions at orbital separations between $\sim100$ and 5000 AU with masses as low as 0.05 $M_{\odot}$, while a deep near field search of 86 white dwarfs was capable of directly detecting companions at separations between $\sim50$ and 1100 AU with masses as low as 0.02 $M_{\odot}$. Additionally, all white dwarf targets were examined for near-infrared excess emission, a technique capable of detecting companions at arbitrarily close separations down to masses of 0.05 $M_{\odot}$. No brown dwarf candidates were detected, which implies a brown dwarf companion fraction of $<0.5$% for white dwarfs. In contrast, the stellar companion fraction of white dwarfs as measured by this survey is 22%, uncorrected for bias. Moreover, most of the known and suspected stellar companions to white dwarfs are low mass stars whose masses are only slightly greater than the masses of brown dwarfs. Twenty previously unknown stellar companions were detected, five of which are confirmed or likely white dwarfs themselves, while fifteen are confirmed or likely low mass stars. Similar to the distribution of cool field dwarfs as a function of spectral type, the number of cool unevolved dwarf companions peaks at mid-M type. Based on the present work, relative to this peak, field L dwarfs appear to be roughly 2-3 times more abundant than companion L dwarfs. Additionally, there is no evidence that the initial companion masses have been altered by post main sequence binary interactions.Comment: 149 pages, 59 figures, 11 tables, accepted to ApJ Supplement

Design and investigation of a test rig based on AI smart vi-sion sensors for automated component inspection of press-hardened car body components

Defects such as cracks, overlaps and impressions occur during the production of press-hardened car body components. At present, these types of defects are counteracted in the industrial environment by costly visual inspections carried out by humans. Due to the poor efficiency of visual inspection compared to automated inspection and the risk of defects not being detected, the use of AI-based smart vision sensors is being evaluated in order to enable an automated component inspection process with their help. For the realisation of the test, the most relevant defect types deformation, crack and overlap are identified using a Pareto analysis

Physics-Informed Machine Learning for the Inverse Design of Wave Scattering Clusters

Clusters of wave-scattering oscillators offer the ability to passively control wave energy in elastic continua. However, designing such clusters to achieve a desired wave energy pattern is a highly nontrivial task. While the forward scattering problem may be readily analyzed, the inverse problem is very challenging as it is ill-posed, high-dimensional, and known to admit non-unique solutions. Therefore, the inverse design of multiple scattering fields and remote sensing of scattering elements remains a topic of great interest. Motivated by recent advances in physics-informed machine learning, we develop a deep neural network that is capable of predicting the locations of scatterers by evaluating the patterns of a target wavefield. We present a modeling and training formulation to optimize the multi-functional nature of our network in the context of inverse design, remote sensing, and wavefield engineering. Namely, we develop a multi-stage training routine with customized physics-based loss functions to optimize models to detect the locations of scatterers and predict cluster configurations that are physically consistent with the target wavefield. We demonstrate the efficacy of our model as a remote sensing and inverse design tool for three scattering problem types, and we subsequently applicability for designing clusters that direct waves along preferred paths or localize wave energy. Hence, we present an effective model for multiple scattering inverse design which may have diverse applications such as wavefield imaging or passive wave energy control.Comment: 27 pages of main text; 41 pages tota

Konzeption und Untersuchung eines Prüfstandes auf der Basis von KI-Smart-Vision-Sensoren für die automatisierte Bauteilprüfung pressgehärteter Karosseriebauteile

Bei der Herstellung pressgehärteter Karosseriebauteile treten Fehler wie Risse, Überlappungen und Abdrücke auf. Gegenwärtig wird diesen Fehlerarten im industriellen Umfeld durch kostenaufwändige, von Menschen durchgeführte Sichtkontrollen entgegengewirkt. Aufgrund des schlechten Wirkungsgrades der visuellen Prüfung gegenüber einer automatisierten Prüfung und der Gefahr des Nichterkennens von Fehlern, wird der Einsatz von KI-basierten Smart-Vision-Sensoren evaluiert, um mit deren Hilfe einen automatisierten Bauteilprüfprozess zu ermöglichen

Initial-Final Mass Relationship for Stars of Different Metallicities

Following Paczy\'{n}ski & Zi\'{o}lkowski (1968) and Han et al. (1994), we assume that the envelope of an asymptotic giant branch (AGB) or a first giant branch (FGB) star is lost when the binding energy of the envelope is equal to zero ($\Delta W=0$) and the core mass of the AGB star or the FGB star at the point ($\Delta W=0$) is taken as the final mass. Using this assumption, we calculate the IFMRs for stars of different metallicities.We find that the IFMRs depends strongly on the metallicity, i.e. $Z=0.0001, 0.0003, 0.001, 0.004, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.08$ and 0.1. From $Z=0.04$, the final mass of the stars with a given initial mass increases with increasing or decreasing metallicity. The difference of the final mass due to the metallicity may be up to 0.4 $M_{\odot}$. A linear fit of the initial-final mass relationship in NGC 2099 (M37) shows a potential evidence of the effect of metallicity on the IFMR. The IFMR for stars of $Z=0.02$ obtained in the paper matches well with those inferred observationally in the Galaxy. For $Z\geq 0.02$, helium WDs are obtained from the stars of $M_{\rm i}\leq 1.0 M_{\odot}$ and this result is upheld by the discovery of numerous low-mass WDs in NGC 6791 which is a metal-rich old open cluster. Using the IFMR for stars of $Z=0.02$ obtained in the paper, we have reproduced the mass distribution of DA WDs in Sloan DR4 except for some ultra-massive white dwarfs. The trend that the mean mass of WDs decreases with effective temperature may originate from the increase of the initial metallicities of stars. We predict that metal-rich low-mass stars may become under-massive white dwarfs.Comment: 14 pages, 8 figures, accepted for publication in A&

Transcriptional repressor ZEB2 promotes terminal differentiation of CD8⁺ effector and memory T cell populations during infection

ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition-dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is up-regulated by activated T cells, specifically in the KLRG1(hi) effector CD8(+) T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8(+) T cells after primary and secondary infection with a severe impairment in the generation of the KLRG1(hi) effector memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress Il7r and Il2 in CD8(+) T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box sites in the Zeb2 gene and that T-bet and ZEB2 regulate similar gene expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Collectively, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8(+) T cells

Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis.

Angiogenesis and the development of a vascular network are required for tumour progression, and they involve the release of angiogenic factors, including vascular endothelial growth factor (VEGF-A), from both malignant and stromal cell types. Infiltration by cells of the myeloid lineage is a hallmark of many tumours, and in many cases the macrophages in these infiltrates express VEGF-A. Here we show that the deletion of inflammatory-cell-derived VEGF-A attenuates the formation of a typical high-density vessel network, thus blocking the angiogenic switch in solid tumours in mice. Vasculature in tumours lacking myeloid-cell-derived VEGF-A was less tortuous, with increased pericyte coverage and decreased vessel length, indicating vascular normalization. In addition, loss of myeloid-derived VEGF-A decreases the phosphorylation of VEGF receptor 2 (VEGFR2) in tumours, even though overall VEGF-A levels in the tumours are unaffected. However, deletion of myeloid-cell VEGF-A resulted in an accelerated tumour progression in multiple subcutaneous isograft models and an autochthonous transgenic model of mammary tumorigenesis, with less overall tumour cell death and decreased tumour hypoxia. Furthermore, loss of myeloid-cell VEGF-A increased the susceptibility of tumours to chemotherapeutic cytotoxicity. This shows that myeloid-derived VEGF-A is essential for the tumorigenic alteration of vasculature and signalling to VEGFR2, and that these changes act to retard, not promote, tumour progression

Einfluss von Impfungen und Kontaktreduktionen auf die dritte Welle der SARS-CoV-2-Pandemie und perspektivische Rückkehr zu prä-pandemischem Kontaktverhalten

Das im Epidemiologischen Bulletin 13/2021 vorgestellte mathematische Modell schätzt die voraussichtlichen Effekte der COVID-19-Impfung in der Bevölkerung in Deutschland und vergleicht mögliche Strategien zur Priorisierung einzelner Bevölkerungsgruppen bei Knappheit der verfügbaren Impfstoffdosen. Das Modell ermöglicht nicht nur die Abbildung des aktuellen Infektionsgeschehens, sondern kann über Fragestellungen zur Impfstrategie hinaus auch Strategien zur Lockerung der bestehenden bzw. die Wiederaufnahme von Kontaktbeschränkungen analysieren. Dabei können saisonale Effekte auf die Übertragung von SARS-CoV-2 sowie der Einfluss neuer Virusvarianten berücksichtigt werden

Planning of organizational changes

This article examines the importance of planning the activity to the head, especially during periods of active changes of operating principles in all possible company existence stages. A logical link is carried out between specific changes within the selected process: either with related activities or with the whole company structure organization. The author argues that the effective communication should be in the company and outside it to build a successful business.Данная статья показывает важность планирования своей деятельности как руководителя, особенно в периоды проведения активных изменений принципов работы, на всех возможных этапах существования компании, а также проводится логическая связь между конкретными изменениями внутри выбранного процесса не только со смежными направлениями деятельности, но и со организацией структуры компании в целом. Речь также идет о влиянии эффективных коммуникаций, внутри компании и за ее пределами, для построения успешного бизнеса и карьеры менеджера в целом. Данная статья будет полезна для начинающих руководителей всех типов компаний