Palaeolimnology of Lake Sapanca and identification of historic earthquake signals, Northern Anatolian Fault Zone (Turkey)

Lake Sapanca is located on a strand of the Northern Anatolian Fault Zone (NAFZ, Turkey), where a series of strong earthquakes (Ms >6.0) have occurred over the past hundred years. Identifying prehistoric earthquakes in and around Lake Sapanca is key to a better understanding of plate movements along the NAFZ. This study contributes to the development of palaeolimnological tools to identify past earthquakes in Lake Sapanca. To this end several promising proxies were investigated, specifically lithology, magnetic susceptibility, grain size (thin-section and laser analysis), geochemistry, pollen concentration, diatom assemblages, 137Cs and 210Pb. Sedimentological indicators provided evidence for reworked, turbidite-like or homogeneous facies (event layers) in several short cores (<45 cm). Other indicators of sediment input and the historical chronicles available for the area suggest that three of these event layers likely originated from the AD 1957, 1967 and 1999 earthquakes. Recent changes in sediment deposition and nutrient levels have also been identified, but are probably not related to earthquakes. This study demonstrates that a combination of indicators can be used to recognize earthquake-related event layers in cores that encompass a longer period of time

Putative Cooperative ATP-DnaA Binding to Double-Stranded DnaA Box and Single-Stranded DnaA-Trio Motif upon Helicobacter pylori Replication Initiation Complex Assembly

oriC is a region of the bacterial chromosome at which the initiator protein DnaA interacts with specific sequences, leading to DNA unwinding and the initiation of chromosome replication. The general architecture of oriCs is universal; however, the structure of oriC and the mode of orisome assembly differ in distantly related bacteria. In this work, we characterized oriC of Helicobacter pylori, which consists of two DnaA box clusters and a DNA unwinding element (DUE); the latter can be subdivided into a GC-rich region, a DnaA-trio and an AT-rich region. We show that the DnaA-trio submodule is crucial for DNA unwinding, possibly because it enables proper DnaA oligomerization on ssDNA. However, we also observed the reverse effect: DNA unwinding, enabling subsequent DnaA–ssDNA oligomer formation—stabilized DnaA binding to box ts1. This suggests the interplay between DnaA binding to ssDNA and dsDNA upon DNA unwinding. Further investigation of the ts1 DnaA box revealed that this box, together with the newly identified c-ATP DnaA box in oriC1, constitute a new class of ATP–DnaA boxes. Indeed, in vitro ATP–DnaA unwinds H. pylori oriC more efficiently than ADP–DnaA. Our results expand the understanding of H. pylori orisome formation, indicating another regulatory pathway of H. pylori orisome assembly

Photoreduction of CO2 with a Formate Dehydrogenase Driven by Photosystem II Using a Semi-artificial Z-Scheme Architecture.

Solar-driven coupling of water oxidation with CO2 reduction sustains life on our planet and is of high priority in contemporary energy research. Here, we report a photoelectrochemical tandem device that performs photocatalytic reduction of CO2 to formate. We employ a semi-artificial design, which wires a W-dependent formate dehydrogenase (FDH) cathode to a photoanode containing the photosynthetic water oxidation enzyme, Photosystem II, via a synthetic dye with complementary light absorption. From a biological perspective, the system achieves a metabolically inaccessible pathway of light-driven CO2 fixation to formate. From a synthetic point of view, it represents a proof-of-principle system utilizing precious-metal-free catalysts for selective CO2-to-formate conversion using water as an electron donor. This hybrid platform demonstrates the translatability and versatility of coupling abiotic and biotic components to create challenging models for solar fuel and chemical synthesis.ERC Consolidator Grant, EPSRC, Christian Doppler Research Association (Austrian Federal Ministry for Digital and Economic Affairs and the National Foundation for Research, Technology and Development), the OMV group, Deutsche Forschungsgemeinschaft, European Union's Horizon 2020 MSCA, Fundação para a Ciência e Tecnologia (Portugal), COMPETE2020/POCI and European Union’s Horizon 202

Endocrine control of canine mammary neoplasms: serum reproductive hormone levels and tissue expression of steroid hormone, prolactin and growth hormone receptors

BACKGROUND: Neoplasms of the mammary gland are among the most common diseases in female domestic dogs (Canis familiaris). It is assumed that reproductive hormones influence tumorigenesis in this species, although the precise role of the endocrine milieu and reproductive state is subject to continuing discussion. In line with this, a recent systematic review of available data on the development of mammary neoplasms revealed weak evidence for risk reduction after neutering and an effect of age at neutering. Investigation of several hormone receptors has revealed decreased expression of estrogen receptor-alpha (ERα, ESR1), progesterone (P4) receptor (PGR), prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) associated with neoplastic differentiation of mammary tissues. In other studies, increased levels of estrogens, progesterone and prolactin were found in serum and/or tissue homogenates of dogs with malignant neoplasms. However, the association between these entities within one animal population was never previously examined. Therefore, this study investigated the association between circulating serum concentrations of estradiol-17β, progesterone and prolactin, and gene expression of ERα (ESR1), ERβ (ESR2), PGR, PRLR, PRL and GHR, with respect to reproductive state (spayed vs. intact) and cycle stage (anestrus vs. diestrus). Additionally, the expression of E-cadherin (CDH-1) was evaluated as a possible indicator of metastatic potential. RESULTS: For all receptors, the lowest gene expression was found in malignant tumors compared to normal tissues of affected dogs. Steroid levels were not influenced by their corresponding receptor expression in mammary neoplasms, but increased PRL levels were negatively associated with low PRLR gene expression in malignant tumors. The expression of CDH-1 was influenced by tumor malignancy and cycle stage, i.e., the highest gene expression was found in benign mammary tumors in diestrous dogs compared to normal and malignant mammary tissues of anestrous and spayed dogs. CONCLUSIONS: Herein, it has been confirmed that transformation towards malignant neoplasms is associated with significant reduction of gene expression of particular hormone receptors. Only PRLR in malignant tumors seems to be influenced by circulating PRL levels. In dogs, CDH-1 can be used as a prognostic factor; its expression, however, in benign tumors is influenced by cycle stage

Engineering of NADPH Supply Boosts Photosynthesis-Driven Biotransformations

was reached, allowing the complete conversion of a 60 mM substrate solution within 4 h

Explainable Predictive Maintenance

Explainable Artificial Intelligence (XAI) fills the role of a critical interface fostering interactions between sophisticated intelligent systems and diverse individuals, including data scientists, domain experts, end-users, and more. It aids in deciphering the intricate internal mechanisms of ``black box'' Machine Learning (ML), rendering the reasons behind their decisions more understandable. However, current research in XAI primarily focuses on two aspects; ways to facilitate user trust, or to debug and refine the ML model. The majority of it falls short of recognising the diverse types of explanations needed in broader contexts, as different users and varied application areas necessitate solutions tailored to their specific needs. One such domain is Predictive Maintenance (PdM), an exploding area of research under the Industry 4.0 \& 5.0 umbrella. This position paper highlights the gap between existing XAI methodologies and the specific requirements for explanations within industrial applications, particularly the Predictive Maintenance field. Despite explainability's crucial role, this subject remains a relatively under-explored area, making this paper a pioneering attempt to bring relevant challenges to the research community's attention. We provide an overview of predictive maintenance tasks and accentuate the need and varying purposes for corresponding explanations. We then list and describe XAI techniques commonly employed in the literature, discussing their suitability for PdM tasks. Finally, to make the ideas and claims more concrete, we demonstrate XAI applied in four specific industrial use cases: commercial vehicles, metro trains, steel plants, and wind farms, spotlighting areas requiring further research.Comment: 51 pages, 9 figure

Selected Uterine Immune Events Associated With the Establishment of Pregnancy in the Dog

In the dog, implantation takes place at approximately 17 days of embryonal life and, while exposed to relatively high circulating progesterone concentrations, embryos presence is required for the formation of decidua. Furthermore, a balance between pro- and anti-inflammatory responses in conceptus-maternal communication is crucial for the onset of pregnancy. Strikingly, the understanding of such immune mechanisms in canine reproduction is still elusive. Here, canine uterine samples from pre-implantation (day 10–12, E+) and corresponding non-pregnant controls (E–), implantation (day 17,Imp) and post-implantation (day 18–25, Post-Imp) stages of pregnancy were used to investigate the expression and localization of several immune-related factors. The most important findings indicate increased availability of CD4, MHCII, NCR1, IDO1, AIF1, CD25, CCR7, and IL6 in response to embryo presence (E+), while FoxP3 and CCL3 were more abundant in E– samples. Implantation was characterized by upregulated levels of FoxP3, IL12a, ENG, and CDH1, whereas CD4, CCR7, IL8, and -10 were less represented. Following implantation, decreased transcript levels of TNFR1, MHCII, NCR1, TLR4, CD206, FoxP3, and IL12a were observed concomitantly with the highest expression of IL6 and IL1β. MHCII, CD86, CD206, CD163, TNFa, IDO1, and AIF1 were immunolocalized in macrophages, CD4 and Nkp46 in lymphocytes, and some signals of IDO1, AIF1, and TNF-receptors could also be identified in endothelial cells and/or uterine glands. Cumulatively, new insights regarding uterine immunity in the peri-implantation period are provided, with apparent moderated pro-inflammatory signals prevailing during pre-implantation, while implantation and early trophoblast invasion appear to beassociated with immunomodulatory and rather anti-inflammatory conditions

QSAR studies on a number of pyrrolidin-2-one antiarrhythmic arylpiperazinyls

The activity of a number of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one antiarrhythmic (AA) agents was described using the quantitative structure–activity relationship model by applying it to 33 compounds. The molecular descriptors of the AA activity were obtained by quantum chemical calculations combined with molecular modeling calculations. The resulting model explains up to 91% of the variance and it was successfully validated by four tests (LOO, LMO, external test, and Y-scrambling test). Statistical analysis shows that the AA activity of the studied compounds depends mainly on the PCR and JGI4 descriptors

Impact processes, permafrost dynamics, and climate and environmental variability in the terrestrial Arctic as inferred from the unique 3.6 Myr record of Lake El'gygytgyn, Far East Russia – A review

© 2016 Elsevier LtdLake El'gygytgyn in Far East Russia is a 3.6 Myr old impact crater lake. Located in an area that has never been affected by Cenozoic glaciations nor desiccation, the unique sediment record of the lake represents the longest continuous sediment archive of the terrestrial Arctic. The surrounding crater is the only impact structure on Earth developed in mostly acid volcanic rocks. Recent studies on the impactite, permafrost, and sediment sequences recovered within the framework of the ICDP “El'gygytgyn Drilling Project” and multiple pre-site surveys yielded new insight into the bedrock origin and cratering processes as well as permafrost dynamics and the climate and environmental history of the terrestrial Arctic back to the mid-Pliocene. Results from the impact rock section recovered during the deep drilling clearly confirm the impact genesis of the El'gygytgyn crater, but indicate an only very reduced fallback impactite sequence without larger coherent melt bodies. Isotope and element data of impact melt samples indicate a F-type asteroid of mixed composition or an ordinary chondrite as the likely impactor. The impact event caused a long-lasting hydrothermal activity in the crater that is assumed to have persisted for c. 300 kyr. Geochemical and microbial analyses of the permafrost core indicate a subaquatic formation of the lower part during lake-level highstand, but a subaerial genesis of the upper part after a lake-level drop after the Allerød. The isotope signal and ion compositions of ground ice is overprinted by several thaw-freeze cycles due to variations in the talik underneath the lake. Modeling results suggest a modern permafrost thickness in the crater of c. 340 m, and further confirm a pervasive character of the talik below Lake El'gygytgyn. The lake sediment sequences shed new leight into the Pliocene and Pleistocene climate and environmental evolution of the Arctic. During the mid-Pliocene, significantly warmer and wetter climatic conditions in western Beringia than today enabled dense boreal forests to grow around Lake El'gygytgyn and, in combination with a higher nutrient flux into the lake, promoted primary production. The exceptional warmth during the mid-Pliocene is in accordance with other marine and terrestrial records from the Arctic and indicates a period of enhanced “Arctic amplification”. The favourable conditions during the mid-Pliocene were repeatedly interrupted by climate deteriorations, e.g., during Marine Isotope Stage (MIS) M2, when pollen data and sediment proxies indicate a major cooling and the onset of local permafrost around the lake. A gradual vegetation change after c. 3.0 Ma points to the onset of a long-term cooling trend during the Late Pliocene that culminated in major temperature drops, first during MIS G6, and later during MIS 104. These cold events coincide with the onset of an intensified Northern Hemisphere (NH) glaciation and the largest extent of the Cordilleran Ice Sheet, respectively. After the Pliocene/Pleistocene transition, local vegetation and primary production in Lake El'gygtygyn experienced a major change from relatively uniform conditions to a high-amplitude glacial-to-interglacial cyclicity that fluctuated on a dominant 41 kyr obliquity band, but changed to a 100 kyr eccentricity dominance during the Middle Pleistocene transition (MPT) at c. 1.2–0.6 Ma. Periods of exceptional warming in the Pleistocene record of Lake El'gygytgyn with dense boreal forests around and peaks of primary production in the lake are assigned to so-called “super-interglacial” periods. The occurrence of these super-interglacials well corresponds to collapses of the West Antarctic Ice Sheet (WAIS) recorded in ice-free periods in the ANDRILL core, which suggests strong intrahemispheric teleconnections presumably driven by changes in the thermocline ocean circulation

Antiarrhythmic and antioxidant activity of novel pyrrolidin-2-one derivatives with adrenolytic properties

A series of novel pyrrolidin-2-one derivatives (17 compounds) with adrenolytic properties was evaluated for antiarrhythmic, electrocardiographic and antioxidant activity. Some of them displayed antiarrhythmic activity in barium chloride-induced arrhythmia and in the rat coronary artery ligation-reperfusion model, and slightly decreased the heart rate, prolonged P–Q, Q–T intervals and QRS complex. Among them, compound EP-40 (1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one showed excellent antiarrhythmic activity. This compound had significantly antioxidant effect, too. The present results suggest that the antiarrhythmic effect of compound EP-40 is related to their adrenolytic and antioxidant properties. A biological activity prediction using the PASS software shows that compound EP-35 and EP-40 can be characterized by antiischemic activity; whereas, compound EP-68, EP-70, EP-71 could be good tachycardia agents