Einsatzgebiete und Anwendungsfälle von Künstlicher Intelligenz in der Wertschöpfungskette der zehn größten Medienunternehmen Deutschlands

Künstliche Intelligenz (KI) hat sich in den letzten Jahren zu einer der bedeutendsten Technologien entwickelt. Angesichts der symbiotischen Verbindung zwischen Medienbranche und technologischem Fortschritt sowie dessen weitreichenden Auswirkungen insbesondere auf die Wertschöpfungskette, hat dieser Beitrag das Ziel, den Einsatz von KI und deren Anwendungen im Rahmen der Wertschöpfungsketten der zehn größten deutschen Medienunternehmen zu betrachten. Fasst man die wichtigsten Erkenntnisse zusammen, so sind im Untersuchungszeitraum die Wertschöpfungsstufen Beschaffung von Inhalten sowie Distribution die Wertschöpfungsstufen, die in den untersuchten Medienunternehmen am stärksten von KI betroffen sind. Die häufigsten Anwendungsfälle sind Vorlesefunktionen, Sprachassistenten und Chatbots (als Teil der Wertschöpfungsstufe Distribution). Natural Language Processing sowie Sprachassistenten und Speech Recognition sind die KI-Technologien, die insgesamt in den untersuchten Unternehmen zum Untersuchungszeitpunkt am häufigsten eingesetzt werden. ProSiebenSat.1, Bertelsmann, Axel Springer sowie ARD sind die Unternehmen, die im Untersuchungszeitraum hinsichtlich KI-Einsatz am bereitesten aufgestellt sind - breit sowohl hinsichtlich der betroffenen Wertschöpfungsstufen, als auch hinsichtlich der Vielfalt an unterschiedlichen eingesetzten KI-Technologien.Artificial Intelligence (AI) has become one of the most important technologies in recent years. Given the symbiotic relationship between the media industry and technological progress and its far- reaching impact on the value chain in particular, this paper aims to look at the use of AI and its applications in the value chains of the ten largest German media companies. Summarizing the most important findings, the value creation stages of content procurement and distribution are the stages most affected by AI in the media companies studied during the period under review. The most common use cases are read-aloud functions, voice assistants and chatbots (as part of the distribution value chain). Natural Language Processing as well as Speech Assistants and Speech Recognition are the AI technologies that are most frequently used overall in the companies studied at the time of the study. ProSiebenSat.1, Bertelsmann, Axel Springer and ARD are the companies that are most prepared to use AI in the period under review - broadly speaking, both in terms of the value creation stages involved and in terms of the variety of different AI technologies used

Reciprocal regulation of the cholinic phenotype and epithelial-mesenchymal transition in glioblastoma cells

Glioblastoma (GBM) is the most malignant brain tumor with very limited therapeutic options. Standard multimodal treatments, including surgical resection and combined radio-chemotherapy do not target the most aggressive subtype of glioma cells, brain tumor stem cells (BTSCs). BTSCs are thought to be responsible for tumor initiation, progression, and relapse. Furthermore, they have been associated with the expression of mesenchymal features as a result of epithelial-mesenchymal transition (EMT) thereby inducing tumor dissemination and chemo resistance. Using high resolution proton nuclear magnetic resonance spectroscopy (1H NMR) on GBM cell cultures we provide evidence that the expression of well-known EMT activators of the ZEB, TWIST and SNAI families and EMT target genes N-cadherin and VIMENTIN is associated with aberrant choline metabolism. The cholinic phenotype is characterized by high intracellular levels of phosphocholine and total choline derivatives and was associated with malignancy in various cancers. Both genetic and pharmacological inhibition of the cardinal choline metabolism regulator choline kinase alpha (CHKα) significantly reduces the cell viability, invasiveness, clonogenicity, and expression of EMT associated genes in GBM cells. Moreover, in some cell lines synergetic cytotoxic effects were observed when combining the standard of care chemotherapeutic temozolomide with the CHKα inhibitor V-11-0711. Taken together, specific inhibition of the enzymatic activity of CHKα is a powerful strategy to suppress EMT which opens the possibility to target chemo-resistant BTSCs through impairing their mesenchymal transdifferentiation. Moreover, the newly identified EMT-oncometabolic network may be helpful to monitor the invasive properties of glioblastomas and the success of anti-EMT therapy

A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity

Abstract: Cancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply of macromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy in cancer therapy. Several tumors excessively metabolize glutamine to generate precursors for nonessential amino acids, nucleotides, and lipids, in a process called glutaminolysis. Here we show that pharmacological inhibition of glutaminase (GLS) eradicates glioblastoma stem-like cells (GSCs), a small cell subpopulation in glioblastoma (GBM) responsible for therapy resistance and tumor recurrence. Treatment with small molecule inhibitors compound 968 and CB839 effectively diminished cell growth and in vitro clonogenicity of GSC neurosphere cultures. However, our pharmaco-metabolic studies revealed that only CB839 inhibited GLS enzymatic activity thereby limiting the influx of glutamine derivates into the TCA cycle. Nevertheless, the effects of both inhibitors were highly GLS specific, since treatment sensitivity markedly correlated with GLS protein expression. Strikingly, we found GLS overexpressed in in vitro GSC models as compared with neural stem cells (NSC). Moreover, our study demonstrates the usefulness of in vitro pharmaco-metabolomics to score target specificity of compounds thereby refining drug development and risk assessment

A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity

Abstract: Cancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply of macromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy in cancer therapy. Several tumors excessively metabolize glutamine to generate precursors for nonessential amino acids, nucleotides, and lipids, in a process called glutaminolysis. Here we show that pharmacological inhibition of glutaminase (GLS) eradicates glioblastoma stem-like cells (GSCs), a small cell subpopulation in glioblastoma (GBM) responsible for therapy resistance and tumor recurrence. Treatment with small molecule inhibitors compound 968 and CB839 effectively diminished cell growth and in vitro clonogenicity of GSC neurosphere cultures. However, our pharmaco-metabolic studies revealed that only CB839 inhibited GLS enzymatic activity thereby limiting the influx of glutamine derivates into the TCA cycle. Nevertheless, the effects of both inhibitors were highly GLS specific, since treatment sensitivity markedly correlated with GLS protein expression. Strikingly, we found GLS overexpressed in in vitro GSC models as compared with neural stem cells (NSC). Moreover, our study demonstrates the usefulness of in vitro pharmaco-metabolomics to score target specificity of compounds thereby refining drug development and risk assessment

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Oral Treatment with <span style="font-variant: small-caps">d</span>-RD2RD2 Impedes Early Disease Mechanisms in SOD1*G93A Transgenic Mice but Does Not Prolong Survival

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons, thus, progressing to complete muscle loss until the patient dies from respiratory arrest. The disease is not curable, and patients die approximately 2–5 years after diagnosis. Studying the underlying disease mechanisms to get access to new treatment options is, therefore, essential for patients’ benefit. However, so far, only three drugs that alleviate the symptoms have been approved by the U.S. Food and Drug Administration (FDA). A new drug candidate for the treatment of ALS is the all-d-enantiomeric peptide RD2RD2. In this study, we investigated the therapeutic effect of RD2RD2 in two setups. First, we analyzed disease progression and survival in 7 week-old B6.Cg-Tg(SOD1*G93A)1Gur/J mice. Second, we confirmed the result of the survival analysis in the B6SJL-Tg(SOD1*G93A)1Gur/J mouse line. Shortly before disease onset, the mice were treated daily with an oral dose of 50 mg/kg body weight. Treatment with RD2RD2 led to a delayed disease onset and reduced motor phenotype as shown using the SHIRPA test, the splay reflex test, and the pole test, but did not affect survival. In conclusion, RD2RD2 has the ability to delay the onset of symptoms

The effect of neurosphere culture conditions on the cellular metabolism of glioma cells

Glioblastoma (GBM) is the most common and lethal adult glial brain tumour, with a mean overall survival of 16-19 months after primary diagnosis under the current standard-of-care treatment scheme [26]. Despite enormous research efforts towards early diagnosis and more efficient treatment, the prognosis of GBMs remains dismal.The influence of culture conditions has been wi­dely investigated in the field of glioma research, suggesting that neurosphere cultures, compared to adherent growth, more closely resemble the original patient’s tumour [29] showing high stem cell compartment [1] and therefore are more suitable for testing of novel therapeutic spectras approaches [30]. In this report we describe altered relative concentrations of the cholines, creatine, myo-inositol, and glycine in the human GBM cell line U87 propagated under stem cell conditions as compared to classical monolayer culture. Furthermore, U87 neurospheres showed significant higher levels of the putative GBM stem cell marker CD133 as their serum-propagated counterparts. Detection and targeting of miss-regulated choline-, myo-inosi­tol-, creatine-, and glycine-metabolism has been de­s­cribed to have potential utility in the diagnosis and treatment of malignant gliomas [2-4,13,16,19].This is, to our knowledge, the hitherto first link of changes in those oncometabolites [4,25] to variations in cell culture conditions of glioma cells. Inter spectral co-analysis of metabolite concentrations under the two propagation conditions identified reductions in ratios of phosphocholine to glycerophosphocholine (PC/GPC) and glycine to total choline (Gly/tCho) but increases in the quotient of total choline to total creatine (tCho/tCre) and PC/tCre, as well as Gly/myo-inositol (Gly/myo). This work should draw the attention of the scientific community on possible in vitro artefacts and on the need for appropriate models most closely resembling the in vivo biology of investigated tumours