STAT3β is a tumor suppressor in acute myeloid leukemia

Signal transducer and activator of transcription 3 (STAT3) exists in 2 alternatively spliced isoforms, STAT3α and STAT3β. Although truncated STAT3β was originally postulated to act as a dominant-negative form of STAT3α, it has been shown to have various STAT3α-independent regulatory functions. Recently, STAT3β gained attention as a powerful antitumorigenic molecule in cancer. Deregulated STAT3 signaling is often found in acute myeloid leukemia (AML); however, the role of STAT3β in AML remains elusive. Therefore, we analyzed the STAT3β/α messenger RNA (mRNA) expression ratio in AML patients, where we observed that a higher STAT3β/α mRNA ratio correlated with a favorable prognosis and increased overall survival. To gain better understanding of the function of STAT3β in AML, we engineered a transgenic mouse allowing for balanced Stat3β expression. Transgenic Stat3β expression resulted in decelerated disease progression and extended survival in PTEN- and MLL-AF9-dependent AML mouse models. Our findings further suggest that the antitumorigenic function of STAT3β depends on the tumor-intrinsic regulation of a small set of significantly up- and downregulated genes, identified via RNA sequencing. In conclusion, we demonstrate that STAT3β plays an essential tumor-suppressive role in AML

Anti-CD3 antibody treatment reduces scar formation in a rat model of myocardial infarction

Introduction: Antibody treatment with anti-thymocyte globulin (ATG) has been shown to be cardioprotective. We aimed to evaluate which single anti-T-cell epitope antibody alters chemokine expression at a level similar to ATG and identified CD3, which is a T-cell co-receptor mediating T-cell activation. Based on these results, the effects of anti-CD3 antibody treatment on angiogenesis and cardioprotection were tested in vitro and in vivo. Methods: Concentrations of IL-8 and MCP-1 in supernatants of human peripheral blood mononuclear cell (PBMC) cultures following distinct antibody treatments were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). In vivo, anti-CD3 antibodies or vehicle were injected intravenously in rats subjected to acute myocardial infarction (AMI). Chemotaxis and angiogenesis were evaluated using tube and migration assays. Intracellular pathways were assessed using Western blot. Extracellular vesicles (EVs) were quantitatively evaluated using fluorescence-activated cell scanning, exoELISA, and nanoparticle tracking analysis. Also, microRNA profiles were determined by next-generation sequencing. Results: Only PBMC stimulation with anti-CD3 antibody led to IL-8 and MCP-1 changes in secretion, similar to ATG. In a rat model of AMI, systemic treatment with an anti-CD3 antibody markedly reduced infarct scar size (27.8% (Inter-quartile range; IQR 16.2–34.9) vs. 12.6% (IQR 8.3–27.2); p < 0.01). The secretomes of anti-CD3 treated PBMC neither induced cardioprotective pathways in cardiomyocytes nor pro-angiogenic mechanisms in human umbilical vein endothelial cell (HUVECs) in vitro. While EVs quantities remained unchanged, PBMC incubation with an anti-CD3 antibody led to alterations in EVs miRNA expression. Conclusion: Treatment with an anti-CD3 antibody led to decreased scar size in a rat model of AMI. Whereas cardioprotective and pro-angiogenetic pathways were unaltered by anti-CD3 treatment, qualitative changes in the EVs miRNA expression could be observed, which might be causal for the observed cardioprotective phenotype. We provide evidence that EVs are a potential cardioprotective treatment target. Our findings will also provide the basis for a more detailed analysis of putatively relevant miRNA candidates

Integrated land and water-borne geophysical surveys shed light on the sudden drying of large karst lakes in southern Mexico

Karst water resources play an important role in drinking water supply but are highly vulnerable to even slight changes in climate. Thus, solid and spatially dense geological information is needed to model the response of karst hydrological systems to such changes. Additionally, environmental information archived in lake sediments can be used to understand past climate effects on karst water systems. In the present study, we carry out a multi-methodological geophysical survey to investigate the geological situation and sedimentary infill of two karst lakes (Metzabok and Tzibaná) of the Lacandon Forest in Chiapas, southern Mexico. Both lakes present large seasonal lake-level fluctuations and experienced an unusually sudden and strong lake-level decline in the first half of 2019, leaving Lake Metzabok (maximum depth ∼25 m) completely dry and Lake Tzibaná (depth ∼70 m) with a water level decreased by approx. 15 m. Before this event, during a lake-level high stand in March 2018, we collected water-borne seismic data with a sub-bottom profiler (SBP) and transient electromagnetic (TEM) data with a newly developed floating single-loop configuration. In October 2019, after the sudden drainage event, we took advantage of this unique situation and carried out complementary measurements directly on the exposed lake floor of Lakes Metzabok and Tzibaná. During this second campaign, we collected time-domain induced polarization (TDIP) and seismic refraction tomography (SRT) data. By integrating the multi-methodological data set, we (1) identify 5–6 m thick, likely undisturbed sediment sequences on the bottom of both lakes, which are suitable for future paleoenvironmental drilling campaigns, (2) develop a comprehensive geological model implying a strong interconnectivity between surface water and karst aquifer, and (3) evaluate the potential of the applied geophysical approach for the reconnaissance of the geological situation of karst lakes. This methodological evaluation reveals that under the given circumstances, (i) SBP and TDIP phase images consistently resolve the thickness of the fine-grained lacustrine sediments covering the lake floor, (ii) TEM and TDIP resistivity images consistently detect the upper limit of the limestone bedrock and the geometry of fluvial deposits of a river delta, and (iii) TDIP and SRT images suggest the existence of a layer that separates the lacustrine sediments from the limestone bedrock and consists of collapse debris mixed with lacustrine sediments. Our results show that the combination of seismic methods, which are most widely used for lake-bottom reconnaissance, with resistivity-based methods such as TEM and TDIP can significantly improve the interpretation by resolving geological units or bedrock heterogeneities, which are not visible from seismic data. Only the use of complementary methods provides sufficient information to develop comprehensive geological models of such complex karst environment

The relationship between glucose and the liver-alpha cell axis – A systematic review

Until recently, glucagon was considered a mere antagonist to insulin, protecting the body from hypoglycemia. This notion changed with the discovery of the liver-alpha cell axis (LACA) as a feedback loop. The LACA describes how glucagon secretion and pancreatic alpha cell proliferation are stimulated by circulating amino acids. Glucagon in turn leads to an upregulation of amino acid metabolism and ureagenesis in the liver. Several increasingly common diseases (e.g., non-alcoholic fatty liver disease, type 2 diabetes, obesity) disrupt this feedback loop. It is important for clinicians and researchers alike to understand the liver-alpha cell axis and the metabolic sequelae of these diseases. While most of previous studies have focused on fasting concentrations of glucagon and amino acids, there is limited knowledge of their dynamics after glucose administration. The authors of this systematic review applied PRISMA guidelines and conducted PubMed searches to provide results of 8078 articles (screened and if relevant, studied in full). This systematic review aims to provide better insight into the LACA and its mediators (amino acids and glucagon), focusing on the relationship between glucose and the LACA in adult and pediatric subjects

Improving the understanding of transient electromagnetic signals for near-surface applications by assessing the turn-off ramp

The application of the transient electromagnetic (TEM) method to near surface problems depends mainly on the correct resolution of shallow subsurface layers. To resolve the near-surface layers using the TEM method, it is necessary to adjust the obtained signals using correct turn-off ramp times. Hence, the main aim of this work is the quantification of the turn-off ramp. Furthermore, the ramp times are applied to improve the inversion results for determining correct electrical resistivity logs. Additionally, two case studies with a focus on near surface problems are presented to evaluate the corrected TEM resistivity logs. Within the first case study a brick-clay deposit is investigated to quantify the clay content in the subsurface. The aim of the second case study is to develop a novel methodology to characterize a clayey landslide. The quantification of the turn-off ramp was done by using an oscilloscope to measure the signals within the transmitter loop. The brick clay deposit is investigated using electric and electromagnetic methods and the results are validated by comparison to the clay content measured from in-situ soil samples. The development of a novel methodology to characterize a clayey landslide is based upon the integral application of geophysical and geotechnical methods. By application of seismic refraction tomography, it was possible to delineate unconsolidated areas in the subsurface, while the electrical and electromagnetic methods were able to discriminate between different lithological units. The evaluation of the, in terms of the turn-off ramp, corrected TEM resistivity logs was successful, since the TEM method was able to obtain similar results as the well-established electrical resistivity method. The oscilloscope measurements were repeated at different sites and for multiple measurement configurations to provide a data base of turn-off ramp times, ranging between 0.1 and 10 s.8

A Flexible Single Loop Setup for Water-Borne Transient Electromagnetic Sounding Applications

Water-borne transient electromagnetic (TEM) soundings provide the means necessary to investigate the geometry and electrical properties of rocks and sediments below continental water bodies, such as rivers and lakes. Most water-borne TEM systems deploy separated magnetic transmitter and receiver loop antennas—typically in a central or offset configuration. These systems mostly require separated floating devices with rigid structures for both loop antennas. Here, we present a flexible single-loop TEM system, the light-weight design of which simplifies field procedures. Our system also facilitates the use of different geometries of the loop antenna permitting to adjust the depth of investigation (DOI) and the minimum sounding depth in the field. We measure the turn-off ramp with an oscilloscope and use the DOI to assess the minimum and maximum exploration depth of our single-loop TEM system, respectively. A reduction of the loop-antenna size improves early-time TEM data due to a reduced length of the turn-off ramp, whereas an increase of the loop-antenna size enhances the signal strength at late times, which allows to investigate deeper structures below the lake bed. We illustrate the capabilities of our system with a case study carried out at Lake Langau in Austria. Our results show that our system is capable of reaching a DOI of up to 50 m (with a maximum radius of the circular loop of 11.9&nbsp;m), while it also resolves the water layer down to a minimum thickness of 6.8&nbsp;m (when the radius is reduced to 6.2&nbsp;m)

A visual analytics approach to dynamic social networks

The visualization and analysis of dynamic networks have become increasingly important in several fields, for instance sociology or economics. The dynamic and multi-relational nature of this data poses the challenge of understanding both its topological structure and how it changes over time. In this paper we propose a visual analytics approach for analyzing dynamic networks that integrates: a dynamic layout with user-controlled trade-off between stability and consistency; three temporal views based on different combinations of node-link diagrams (layer superimposition, layer juxtaposition, and two-and-a-halfdimensional view); the visualization of social network analysis metrics; and specific interaction techniques for tracking node trajectories and node connectivity over time. This integration of visual, interactive, and automatic methods supports the multifaceted analysis of dynamically changing networks

Sensitivity analysis of inverted model parameters from transient electromagnetic measurements affected by induced polarization effects

We investigate the application of the distance-based global sensitivity analysis (DGSA) to evaluate the sensitivity of electrical model parameters obtained from transient electromagnetic (TEM) data including induced polarization (IP) effects. We propose novel open-source forward modeling and inversion routines for single-loop TEM data including IP effects with the maximum phase angle model to model the frequency dependence of the complex resistivity. In a first step, we evaluate the accuracy of our forward modeling and inversion routines using numerical studies, where the actual variations of layer thicknesses and resistivities, as well as the frequency dependence of the complex resistivity is known. In a second step, we extend our investigation to field data and apply our approach to three distinct case studies in layered media: 1) a confined aquifer corresponding to conductive non-polarizable media, 2) a graphite deposit corresponding to highly conductive and polarizable anomalies in a resistive host rock and 3) an ice glacier corresponding to highly resistive polarizable media. Our DGSA results reveal that standard depth of investigation (DOI) approaches may overestimate the true sensitivity of the model obtained from the inversion. TEM data collected in conductive layered media without IP effects show reduced sensitivity above the predicted DOI. The case studies in polarizable media demonstrate that the maximum phase angle is more influential on the TEM model response than the relaxation time and dispersion coefficient. Our DGSA results for polarizable media reveal that TEM field data collected at the graphite deposit and at the ice glacier are sensitive to the geometry of the polarizable layer.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Applied Geophysics and Petrophysic

Visual Analysis of Dynamic Networks using Change Centrality

Abstract—The visualization and analysis of dynamic social networks are challenging problems, demanding the simultaneous consideration of relational and temporal aspects. In order to follow the evolution of a network over time, we need to detect not only which nodes and which links change and when these changes occur, but also the impact they have on their neighbourhood and on the overall relational structure. Aiming to enhance the perception of structural changes at both the micro and the macro level, we introduce the change centrality metric. This novel metric, as well as a set of further metrics we derive from it, enable the pairwise comparison of subsequent states of an evolving network in a discrete-time domain. Demonstrating their exploitation to enrich visualizations, we show how these change metrics support the visual analysis of network dynamics. I

Conversion of Xylose into D-Xylitol using Catalytic Transfer Hydrogenation with Formic Acid as H-Donor

d-Xylitol, a biomass-derived sweetener, is increasingly used in cosmetics and pharmaceutical products. The raw material for d-xylitol production, d-xylose, is easily accessible from dissolving pulp production. d-xylitol production involves the heterogeneously catalyzed hydrogenation of d-xylose; this process is energy intensive, as the use of H2 requires high pressure and temperature. This work examined catalytic transfer hydrogenation for xylose conversion into xylitol. Formic acid (FA) was used to replace H2 as the H-donor, as it is easily available, inexpensive, may be obtained from renewable sources, and it avoids the risks associated with the use of high-pressure inflammable gas. A variety of commercially available catalysts were screened to reveal the one enabling the highest yield. The experiments were performed at 40, 80, and 140 °C, with pure xylose as a model compound. Triethylamine (Et3N) was added to ensure sufficient conversion rates. Based on the preliminary studies an experimental design was created (Design Expert®), including the two best performing catalysts Ru/Al2O3 and Ru/C, to investigate the influence of temperature and H-donor and base concentration on xylitol yield. Ru/C resulted in maximum d-xylitol yield of 73.2 % at 100 °C, FA to d-xylose ratio 5:1 and Et3N to FA ratio 0.4