Antarctic sympagic meiofauna in winter: Comparing diversity, abundance and biomass between perennially and seasonally ice-covered regions

This study of Antarctic sympagic meiofauna in pack ice during late winter compares communities between the perennially ice-covered western Weddell Sea and the seasonally ice-covered southern Indian Ocean. Sympagic meiofauna (proto- and metazoans >20 μm) and eggs >20 μm were studied in terms of diversity, abundance and carbon biomass, and with respect to vertical distribution. Metazoan meiofauna had significantly higher abundance and biomass in the western Weddell Sea (medians: 31.1×103 m−2 and 6.53mg m−2, respectively) than in the southern Indian Ocean (medians: 1.0×10 103 m−2and 0.06 mg m−2, respectively). Metazoan diversity was also significantly higher in the western Weddell Sea. Furthermore, the two regions differed significantly in terms of meiofauna community composition, as revealed through multivariate analyses. The overall diversity of sympagic meiofauna was high, and integrated abundance and biomass of total meiofauna were also high in both regions (0.6–178.6×103 m−2 and 0.02–89.70mg m−2, respectively), mostly exceeding values reported earlier from the western Weddell Sea in winter. We attribute the differences in meiofauna communities between the two regions to the older first-year ice and multi-year ice that is present in the western Weddell Sea, but not in the southern Indian Ocean. Our study indicates the significance of perennially ice-covered regions for the establishment of diverse and abundant meiofauna communities. Furthermore, it highlights the potential importance of sympagic meiofauna for the organic matter pool and trophic interactions in sea ice

Superoxide dismutase mutations of familial amyotrophic lateral sclerosis and the oxidative inactivation of calcineurin

AbstractApproximately 10% of all familial cases of amyotrophic lateral sclerosis (fALS) are linked to mutations in the SOD1 gene, which encodes the copper/zinc superoxide dismutase (CuZnSOD). Recently, wild-type CuZnSOD was shown to protect calcineurin, a calcium/calmodulin-regulated phosphoprotein phosphatase, from inactivation by reactive oxygen species. We asked whether the protective effect of CuZnSOD on calcineurin is affected by mutations associated with fALS. For this, we monitored calcineurin activity in the presence of mutant and wild-type SOD. We found that the degree of protection against inactivation of calcineurin by different SOD mutants correlates with the severity of the phenotype associated with the different mutations, suggesting a potential role for calcineurin–SOD1 interaction in the etiology of fALS

Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation

Signals from the microenvironment around a cell are known to influence cell behavior. Material properties, such as biochemical composition and substrate stiffness, are today accepted as significant regulators of stem cell fate. The knowledge of how cell behavior is influenced by 3D geometric cues is, however, strongly limited despite its potential relevance for the understanding of tissue regenerative processes and the design of biomaterials. Here, the role of surface curvature on the migratory and differentiation behavior of human mesenchymal stem cells (hMSCs) has been investigated on 3D surfaces with well-defined geometric features produced by stereolithography. Time lapse microscopy reveals a significant increase of cell migration speed on concave spherical compared to convex spherical structures and flat surfaces resulting from an upward-lift of the cell body due to cytoskeletal forces. On convex surfaces, cytoskeletal forces lead to substantial nuclear deformation, increase lamin-A levels and promote osteogenic differentiation. The findings of this study demonstrate a so far missing link between 3D surface curvature and hMSC behavior. This will not only help to better understand the role of extracellular matrix architecture in health and disease but also give new insights in how 3D geometries can be used as a cell-instructive material parameter in the field of biomaterial-guided tissue regeneration.Peer reviewe

Malt1 protease inactivation efficiently dampens immune responses but causes spontaneous autoimmunity.

The protease activity of the paracaspase Malt1 has recently gained interest as a drug target for immunomodulation and the treatment of diffuse large B-cell lymphomas. To address the consequences of Malt1 protease inactivation on the immune response in vivo, we generated knock-in mice expressing a catalytically inactive C472A mutant of Malt1 that conserves its scaffold function. Like Malt1-deficient mice, knock-in mice had strong defects in the activation of lymphocytes, NK and dendritic cells, and the development of B1 and marginal zone B cells and were completely protected against the induction of autoimmune encephalomyelitis. Malt1 inactivation also protected the mice from experimental induction of colitis. However, Malt1 knock-in mice but not Malt1-deficient mice spontaneously developed signs of autoimmune gastritis that correlated with an absence of Treg cells, an accumulation of T cells with an activated phenotype and high serum levels of IgE and IgG1. Thus, removal of the enzymatic activity of Malt1 efficiently dampens the immune response, but favors autoimmunity through impaired Treg development, which could be relevant for therapeutic Malt1-targeting strategies

Technology roadmap for cold-atoms based quantum inertial sensor in space

Recent developments in quantum technology have resulted in a new generation of sensors for measuring inertial quantities, such as acceleration and rotation. These sensors can exhibit unprecedented sensitivity and accuracy when operated in space, where the free-fall interrogation time can be extended at will and where the environment noise is minimal. European laboratories have played a leading role in this field by developing concepts and tools to operate these quantum sensors in relevant environment, such as parabolic flights, free-fall towers, or sounding rockets. With the recent achievement of Bose-Einstein condensation on the International Space Station, the challenge is now to reach a technology readiness level sufficiently high at both component and system levels to provide "off the shelf"payload for future generations of space missions in geodesy or fundamental physics. In this roadmap, we provide an extensive review on the status of all common parts, needs, and subsystems for the application of atom-based interferometers in space, in order to push for the development of generic technology components

A REFERENCE ARCHITECTURE OF HUMAN CYBER-PHYSICAL SYSTEMS – PART III: SEMANTIC FOUNDATIONS

he design and analysis of multi-agent human cyber-physical systems in safety-critical or industry-critical domains calls for an adequate semantic foundation capable of exhaustively and rigorously describing all emergent effects in the joint dynamic behavior of the agents that are relevant to their safety and well-behavior. We present such a semantic foundation. This framework extends beyond previous approaches by extending the agent-local dynamic state beyond state components under direct control of the agent and belief about other agents (as previously suggested for understanding cooperative as well as rational behavior) to agent-local evidence and belief about the overall cooperative, competitive, or coopetitive game structure. We argue that this extension is necessary for rigorously analyzing systems of human cyber-physical systems because humans are known to employ cognitive replacement models of system dynamics that are both non-stationary and potentially incongruent. These replacement models induce visible and potentially harmful effects on their joint emergent behavior and the interaction with cyber-physical system components

Highly variable response to cytotoxic chemotherapy in carcinoma-associated fibroblasts (CAFs) from lung and breast

<p>Abstract</p> <p>Background</p> <p>Carcinoma-associated fibroblasts (CAFs) can promote carcinogenesis and tumor progression. Only limited data on the response of CAFs to chemotherapy and their potential impact on therapy outcome are available. This study was undertaken to analyze the influence of chemotherapy on carcinoma-associated fibroblasts (CAFs) <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>The <it>in vivo </it>response of stromal cells to chemotherapy was investigated in 22 neoadjuvant treated breast tumors on tissue sections before and after chemotherapy. Response to chemotherapy was analyzed <it>in vitro </it>in primary cultures of isolated CAFs from 28 human lung and 9 breast cancer tissues. The response was correlated to <it>Mdm2</it>, <it>ERCC1 </it>and <it>TP53 </it>polymorphisms and <it>TP53 </it>mutation status. Additionally, the cytotoxic effects were evaluated in an <it>ex vivo </it>experiment using cultured tissue slices from 16 lung and 17 breast cancer specimens.</p> <p>Results</p> <p>Nine of 22 tumors showed a therapy-dependent reduction of stromal activity. Pathological response of tumor or stroma cells did not correlate with clinical response. Isolated CAFs showed little sensitivity to paclitaxel. In contrast, sensitivity of CAFs to cisplatinum was highly variable with a GI50 ranging from 2.8 to 29.0 μM which is comparable to the range observed in tumor cell lines. No somatic <it>TP53 </it>mutation was detected in any of the 28 CAFs from lung cancer tissue. In addition, response to cisplatinum was not significantly associated with the genotype of <it>TP53 </it>nor <it>Mdm2 </it>and <it>ERCC1 </it>polymorphisms. However, we observed a non-significant trend towards decreased sensitivity in the presence of <it>TP53 </it>variant genotype. In contrast to the results obtained in isolated cell culture, in tissue slice culture breast cancer CAFs responded to paclitaxel within their microenvironment in the majority of cases (9/14). The opposite was observed in lung cancer tissues: only few CAFs were sensitive to cisplatinum within their microenvironment (2/15) whereas a higher proportion responded to cisplatinum in isolated culture.</p> <p>Conclusion</p> <p>Similar to cancer cells, CAF response to chemotherapy is highly variable. Beside significant individual/intrinsic differences the sensitivity of CAFs seems to depend also on the cancer type as well as the microenvironment.</p

A REFERENCES ARCHITECTURE FOR HUMAN CYBER PHYSICAL SYSTEMS - PART II: FUNDAMENTAL DESIGN PRINCIPLES FOR HUMAN-CPS INTERACTION

As automation increases qualitatively and quantitatively in safety-critical human cyber-physical systems, it is becoming more and more challenging to increase the probability or ensure that human operators still perceive key artefacts and comprehend their roles in the system. In the companion paper, we proposed an abstract reference architecture capable of expressing all classes of system-level interactions in human cyber-physical systems. Here we demonstrate how this reference architecture supports the analysis of levels of communication between agents and helps to identify the potential for misunderstandings and misconceptions. We then develop a metamodel for safe human machine interaction. Therefore, we ask what type of information exchange must be supported on what level so that humans and systems can cooperate as a team, what is the criticality of exchanged information, what are timing requirements for such interactions, and how can we communicate highly critical information in a limited time frame in spite of the many sources of a distorted perception. We highlight shared stumbling blocks and illustrate shared design principles, which rest on established ontologies specific to particular application classes. In order to overcome the partial opacity of internal states of agents, we anticipate a key role of virtual twins of both human and technical cooperation partners for designing a suitable communicati

A REFERENCE ARCHITECTURE OF HUMAN CYBER PHYSICAL SYSTEMS PART I: CONCEPTUAL STRUCTURE

We propose a reference architecture of safety-critical or industry-critical human cyber-physical systems (CPSs) capable of expressing essential classes of system-level interactions between CPS and humans relevant for the societal acceptance of such systems. To reach this quality gate, the expressivity of the model must go beyond classical viewpoints such as operational, functional, architectural views and views used for safety and security analysis. The model does so by incorporating elements of such systems for mutual introspections in situational awareness, capabilities, and intentions in order to enable a synergetic, trusted relation in the interaction of humans and CPSs, which we see as a prerequisite for their societal acceptance. The reference architecture is represented as a metamodel incorporating conceptual and behavioral semantic aspects. We illustrate the key concepts of the metamodel with examples from smart grids, cooperative autonomous driving, and crisis manage

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements