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A functional device was developed to immediately show the localization of veins by detecting a temperature increase on the skin directly above them. Our new idea, compared to other developments, is the comparison of temperatures between a small, ideally punctiform, skin area, and a larger circularly surrounding area. This is realized by two infrared temperature sensors, one with a small field of view, and the other one with a larger field of view. The position of the vein is indicated by two laser modules, which beams cross in one spot, when the device is held in a defined distance to the skin. If the device is held over a vein, the laser spot lightens up. The device was tested in ten study participants. Cooling of the skin by disinfectant spray prior to the measurements increases the temperature gradient and thereby improves the efficiency of the device. Temperature profiles of four skin areas of each study participant were measured before and one minute after application of disinfectant spray. After application of disinfectant spray, a temperature difference of more than 0.3 K between a measuring point above a vein and points 15 mm next to this could be found in 36 out of 40 measurements (90%), compared to 26 out of 40 (65%) before disinfection. The mean temperature gradient could be increased from 0.476 K to 1.03 K (p < 0.001).

The article analyses how competition authorities consider sustainability aspects (e.g. the protection of the environment) in merger control proceedings as well as when analyzing a cooperation under the cartel prohibition. So far, these aspects have not played a role in merger control. The reason for this is the authorities’ competition-oriented and effects-based approach, which only considers measurable efficiencies. The same applies to the cartel prohibition. Sustainability will only be relevant for the assessment under Art. 101 (3) TFEU. Legal literature generally agrees with this approach. However, authorities should give more guidance as to how environmental aspects will be considered in the future. [ABSTRACT FROM AUTHOR]

The treatment of melanoma has been markedly improved by the introduction of targeted therapies and checkpoint blockade immunotherapy. Unfortunately, resistance to these therapies remains a limitation. Novel anticancer therapeutics targeting the MCL1 anti‐apoptotic protein have shown impressive responses in haematological cancers but are yet to be evaluated in melanoma. To assess the sensitivity of melanoma to new MCL1 inhibitors, we measured the response of 51 melanoma cell lines to the novel MCL1 inhibitor, S63845. Additionally, we assessed combination of this drug with inhibitors of the bromodomain and extra‐terminal (BET) protein family of epigenetic readers, which we postulated would assist MCL1 inhibition by downregulating anti‐apoptotic targets regulated by NF‐kB such as BCLXL, BCL2A1 and XIAP, and by upregulating pro‐apoptotic proteins including BIM and NOXA. Only 14% of melanoma cell lines showed sensitivity to S63845, however, combination of S63845 and I‐BET151 induced highly synergistic apoptotic cell death in all melanoma lines tested and in an in vivo xenograft model. Cell death was dependent on caspases and BAX/BAK. Although the combination of drugs increased the BH3‐only protein, BIM, and downregulated anti‐apoptotic proteins such as BCL2A1, the importance of these proteins in inducing cell death varied between cell lines. ABT‐199 or ABT‐263 inhibitors against BCL2 or BCL2 and BCLXL, respectively, induced further cell death when combined with S63845 and I‐BET151. The combination of MCL1 and BET inhibition appears to be a promising therapeutic approach for metastatic melanoma, and presents opportunities to add further BCL2 family inhibitors to overcome treatment resistance. What's new? Inducing apoptosis in melanoma has proven difficult due to high expression of multiple anti‐apoptotic proteins. Here, the authors tested the effectiveness of novel anti‐apoptotic protein MCL1 inhibitors against a large panel of melanoma lines and examined the potential to combine them with inhibitors of the BET protein family of epigenetic readers. The results show that combining BET and novel MCL1 inhibitors is highly effective at killing many melanoma cell lines by inducing a pro‐apoptotic state while also targeting MCL1. This novel treatment approach may benefit the large proportion of melanoma patients who fail current treatment with targeted therapies and/or immunotherapies. [ABSTRACT FROM AUTHOR]

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Long-term perturbation of de novo chromatin assembly during DNA replication has profound effects on epigenome maintenance and cell fate. The early mechanistic origin of these defects is unknown. Here, we combine acute degradation of Chromatin Assembly Factor 1 (CAF-1), a key player in de novo chromatin assembly, with single-cell genomics, quantitative proteomics, and live-microscopy to uncover these initiating mechanisms in human cells. CAF-1 loss immediately slows down DNA replication speed and renders nascent DNA hyperaccessible. A rapid cellular response, distinct from canonical DNA damage signaling, is triggered and lowers histone mRNAs. As a result, histone variants usage and their modifications are altered, limiting transcriptional fidelity and delaying chromatin maturation within a single S-phase. This multi-level response induces a cell-cycle arrest after mitosis. Our work reveals the immediate consequences of defective de novo chromatin assembly during DNA replication, explaining how at later times the epigenome and cell fate can be altered.