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Anna Simon-Sickley zeigt in ihrem Beitrag die historischen Verflechtungen des Begriffs des 'Anthropozäns' mit den Diskursen von Energie und Entropie. Die Gefahren einer semantischen Rückprojektion reflektierend, kann sie deutlich machen, wie die heute 'totalisierende Metapher' des Anthropozäns bis in die Diskurse der Energie und Entropie zurückreicht. Energie erscheint dabei begrifflich als Einheitswährung, mittels deren Natur einzig als auszubeutende Ressource (fossile Brennstoffe) thematisiert wird. Mit der Thermodynamik legt die Umweltforschung den Schwerpunkt auf Effizienz, Produktion und Abfall. Das wachsende Bewusstsein, dass Energie Geschichte strukturiert, erweist sich als eine Perspektive, die für die Geschichtsschreibung des Anthropozäns von entscheidender Bedeutung geworden ist. Mit ihm soll sich das wissenschaftliche Thema des Menschen vom Kontext der Geisteswissenschaften zum Kontext der Wissenschaften verschoben haben. Menschliche Systeme und Kulturen werden im Anthropozändiskurs als geologische Kräfte verstanden und erscheinen als geochronologische Epochen naturwissenschaftlich exakt berechenbar.
Rodrigues Ridge connects the Réunion hotspot track with the Central Indian Ridge (CIR) and has been suggested to represent the surface expression of a sub-lithospheric flow channel. From global earthquake catalogues, the seismicity in the region has been associated mainly with events related to the fracture zones at the CIR. However, some segments of the CIR appear void of seismic events. Here, we report on the seismicity recorded at a temporary array of 10 seismic stations operating on Rodrigues Island from September 2014 to June 2016. The array analysis was performed in the time domain by time shifting and stacking the complete waveforms. Event distances were estimated based on a 1-D velocity model and the travel time differences between S and P wave arrivals. We detected and located 63 new events that were not reported by the global networks. Most of the events (51) are located off the CIR and can be classified as intraplate earthquakes. Local magnitudes varied between 1.6 and 3.7. Four seismic clusters were observed that occurred to the west of the spreading segment of the CIR. The Rodrigues Ridge appeared to be aseismic during the period of operation. The lack of seismic activity along both Rodrigues Ridge and the sections of the CIR to the east of Rodrigues may be explained by partially molten upper-mantle material, possibly in relation to the proposed material flow between the Réunion plume and the CIR.
Omkāra to Ek Onkāra
(2020)
Background: Persistent pain in breast cancer survivors is common. Psychological and sleep-related factors modulate perception, interpretation and coping with pain and may contribute to the clinical phenotype. The present analysis pursued the hypothesis that breast cancer survivors form subgroups, based on psychological and sleep-related parameters that are relevant to the impact of pain on the patients’ life.
Methods: We analysed 337 women treated for breast cancer, in whom psychological and sleep-related parameters as well as parameters related to pain intensity and interference had been acquired. Data were analysed by using supervised and unsupervised machine-learning techniques (i) to detect patient subgroups based on the pattern of psychological or sleep-related parameters, (ii) to interpret the detected cluster structure and (iii) to relate this data structure to pain interference and impact on life.
Results: Artificial intelligence-based detection of data structure, implemented as self-organizing neuronal maps, identified two different clusters of patients. A smaller cluster (11.5% of the patients) had comparatively lower resilience, more depressive symptoms and lower extraversion than the other patients. In these patients, life-satisfaction, mood, and life in general were comparatively more impeded by persistent pain.
Conclusions: The results support the initial hypothesis that psychological and sleep-related parameter patterns are meaningful for subgrouping patients with respect to how persistent pain after breast cancer treatments interferes with their life. This indicates that management of pain should address more complex features than just pain intensity. Artificial intelligence is a useful tool in the identification of subgroups of patients based on psychological factors.
Although immune checkpoint inhibitors such as anti-PD-1 antibodies have shown remarkable clinical success in many different tumor types, the proportion of patients benefiting from this treatment option remains low. Therefore, there is a need to sensitize tumors for immune checkpoint blockade. In this study two approaches were tested, a chemoimmunotherapy approach combining PD-1 checkpoint blockade with doxorubicin (DOX) chemotherapy, and ablation of the sphingosine-1-phosphate (S1P) receptor (S1PR4) based on the following rationale. Chemotherapy was shown to induce immune paralysis which contributes to tumor relapse, while PD-1 signaling was shown to facilitate the acquisition of chemoresistance. Thus, combinatorial chemoimmunotherapy is expected to be beneficial by maintaining or even activating anti-tumor immunity during chemotherapy. S1PR4 is an immune cell specific receptor, whose ablation slowed tumor progression by activating anti-tumor immunity in a mouse model that was previously insensitive to anti-PD-1 monotherapy. This suggested that S1PR4 ablation might pre-activate immunity to sensitize for anti-PD-1 therapy.
To test these combinatorial approaches, two tumor mouse models were employed, namely the MC38 murine adenocarcinoma model as well as the transgenic polyoma middle T oncogene (PyMT) breast cancer model. In the MC38 model, a mild synergistic effect of PD-1 immune checkpoint blockade and S1PR4 ablation was observed, indicated by improved tumor progression and survival as compared to the WT control, and an increased number of tumor-free mice compared to anti-PD-1 therapy alone in WT mice. These observations correlated with an enhanced natural killer (NK) cell infiltrate and increased CXCL9 and CXCL10 production in anti-PD-1 treated S1PR4 KO tumors. As noted before, the PyMT model was largely resistant to anti-PD-1 monotherapy in a therapeutic setting. S1PR4 ablation alone showed significant tumor reduction that was not further enhanced by anti-PD-1 treatment. The same was observed when chemotherapy with DOX was added, where WT tumors relapsed, while S1PR4 KO tumor did not. Addition of anti-PD-1 did only mildly increase tumor control in S1PR4 KO mice, indicating that S1PR4 KO per se very efficiently re-activated anti-tumor immunity. Since S1PR4 KO induces type I 12 interferon (IFN-1) over-production in S1PR4 KO PyMT tumors, a link between high IFN-1 levels and tumor immunity was tested by using mice deficient in the IFN-1 receptor (IFNAR1). Unexpectedly, DOX chemotherapy was most efficient in mice with IFNAR ablation only as compared to WT, S1PR4 KO or S1PR4 and IFNAR1 double KO mice, although deficiency in IFNAR signaling is predominantly regarded as tumor promoting. The underlying mechanisms need to be tested in future studies. Interestingly, chemoimmunotherapy in WT mice prevented tumor relapse to a similar extent than S1PR4 KO and was superior to chemotherapy or immune checkpoint blockade alone. To investigate mechanisms of chemoimmunotherapy success compared to monotherapy, whole transcriptome analysis was used, which identified a set of genes that were upregulated specifically upon chemoimmunotherapy. This gene signature and, more specifically, a condensed four-gene signature predicted favorable survival of human mammary carcinoma patients in the METABRIC cohort.
Moreover, PyMT tumors treated with chemoimmunotherapy contained higher levels of cytotoxic lymphocytes, particularly NK cells. Gene set enrichment analysis and ELISA measurements revealed increased IL-27 production and signaling in PyMT tumors upon chemoimmunotherapy. Moreover, IL-27 improved NK cell cytotoxicity against PyMT cells in vitro. These data supported recent clinical observations indicating a benefit of chemoimmunotherapy compared to monotherapy in breast cancer and suggested potential underlying mechanisms.
Taken together the present work revealed new strategies to reactivate tumor immunity leading to improved chemotherapy response, namely a combination with immune checkpoint blockade and ablation of S1PR4, which activated different lymphocyte compartments within tumors.
Despite the success of immune checkpoint blockade in cancer, the number of patients that benefit from this revolutionary treatment option remains low. Therefore, efforts are being undertaken to sensitize tumors for immune checkpoint blockade, which includes combining immune checkpoint blocking agents such as anti-PD-1 antibodies with standard of care treatments. Here we report that a combination of chemotherapy (doxorubicin) and immune checkpoint blockade (anti-PD-1 antibodies) induces superior tumor control compared to chemotherapy and immune checkpoint blockade alone in the murine autochthonous polyoma middle T oncogene-driven (PyMT) mammary tumor model. Using whole transcriptome analysis, we identified a set of genes that were upregulated specifically upon chemoimmunotherapy. This gene signature and, more specifically, a condensed four-gene signature predicted favorable survival of human mammary carcinoma patients in the METABRIC cohort. Moreover, PyMT tumors treated with chemoimmunotherapy contained higher levels of cytotoxic lymphocytes, particularly natural killer cells (NK cells). Gene set enrichment analysis and bead-based ELISA measurements revealed increased IL-27 production and signaling in PyMT tumors upon chemoimmunotherapy. Moreover, IL-27 signaling improved NK cell cytotoxicity against PyMT cells in vitro. Taken together, our data support recent clinical observations indicating a benefit of chemoimmunotherapy compared to monotherapy in breast cancer and suggest potential underlying mechanisms.
Antoinettia, new genus (Coleoptera: Erotylidae: Erotylinae: Tritomini), is erected for three species: A. audbala (Skelley), new combination, A. huhnei Skelley, new species, and A. kovariki (Skelley), new combination. A genus complex involving Ischyrus Lacordaire, 1842, and Megischyrus Crotch, 1873, is defined and a preliminary key to neotropical genera of Tritomini with coarsely facetted eyes is presented.