Explore the vast range of titles available.

We consider a parabolic obstacle problem for Euler’s elastic energy of graphs with fixed ends. We show global existence, well-posedness and subconvergence provided that the obstacle and the initial datum are suitably ‘small’. For symmetric cone obstacles we can improve the subconvergence to convergence. Qualitative aspects such as energy dissipation, coincidence with the obstacle and time regularity are also examined.

Ocean acidification substantially alters ocean carbon chemistry and hence pH but the effects on sea ice formation and the CO2 concentration in the enclosed brine channels are unknown. Microbial communities inhabiting sea ice ecosystems currently contribute 10-50% of the annual primary production of polar seas, supporting overwintering zooplankton species, especially Antarctic krill, and seeding spring phytoplankton blooms. Ocean acidification is occurring in all surface waters but the strongest effects will be experienced in polar ecosystems with significant effects on all trophic levels. Brine algae collected from McMurdo Sound (Antarctica) sea ice was incubated in situ under various carbonate chemistry conditions. The carbon chemistry was manipulated with acid, bicarbonate and bases to produce a pCO2 and pH range from 238 to 6066 µatm and 7.19 to 8.66, respectively. Elevated pCO2 positively affected the growth rate of the brine algal community, dominated by the unique ice dinoflagellate, Polarella glacialis. Growth rates were significantly reduced when pH dropped below 7.6. However, when the pH was held constant and the pCO2 increased, growth rates of the brine algae increased by more than 20% and showed no decline at pCO2 values more than five times current ambient levels. We suggest that projected increases in seawater pCO2, associated with OA, will not adversely impact brine algal communities.

Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells. One method of controlling protein degradation is through the use of degrons. Here the authors present a toolbox of characterised degrons as a library to fine-tune biological gene-expression systems. Its application is demonstrated by a set of tunable synthetic pulse generators in mammalian cells.

This article studies (optimal) W^2m-1,ınfty -regularity for the polyharmonic equation (-)^m u = Q \\; H^n-1 where is a (suitably regular) (n-1) -dimensional submanifold of R^n , H^n-1 is the Hausdorff measure, and Q is some suitably regular density. As an application, we derive (optimal) W^3,ınfty -regularity for solutions of the biharmonic Alt–Caffarelli problem in two dimensions.

This work was funded by the \"European Project on Ocean Acidification\" (EPOCA) (which received funding from the European Community's Seventh Framework Program (FP7/2007-2013) under grant agreement n° 211384) and partly by the Helmholtz Centre for Ocean Research Kiel (GEOMAR) and by the Center of Excellence \"The Future Ocean\" to ML; the Abbey-Santander Internationalization Fund, University of Basque Country (UPV/EHU), and Ministry of Science and Education (Government of Spain) to SBA; the Conselho Nacional de Desenvolvimento Científico e Tecnológico Brasil (CNPq, Processo: 405585/2013-6) to MNM; and ERC-STG-240222PACE for funding HS and AMV. Strains RCC1212 and RCC1258 were obtained from the RCC through the ASSEMBLE program (FP7-227799). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

In synthetic biology, the use of regulatory proteins that bind either DNA or RNA to reprogram mammalian cellular functions allows a variety of computational ‘logic circuits’ to be built in a plug-and-play manner, which may pave the way for precise and robust control of future gene-based and cell-based therapies. Single-cell mammalian biocomputing Synthetic biology is producing genetic circuits of increasing complexity, most of them based on networks derived from microorganisms. Martin Fussenegger and colleagues have turned to mammalian control devices as a basis for the design of a variety of fundamental logic gates. They combine regulatory proteins that bind either DNA or RNA — to control gene transcription or translation, respectively — to reprogram mammalian cellular functions. Through a 'plug-and-play' combination of their basic circuits, they build a variety of computational logic gates (NOT, AND, NAND and N-IMPLY), which could pave the way for precise and robust control of future gene- and cell-based therapies. Synthetic biology has advanced the design of standardized control devices that program cellular functions and metabolic activities in living organisms 1 . Rational interconnection of these synthetic switches resulted in increasingly complex designer networks that execute input-triggered genetic instructions with precision, robustness and computational logic reminiscent of electronic circuits 2 , 3 . Using trigger-controlled transcription factors, which independently control gene expression 4 , 5 , and RNA-binding proteins that inhibit the translation of transcripts harbouring specific RNA target motifs 6 , 7 , we have designed a set of synthetic transcription–translation control devices that could be rewired in a plug-and-play manner. Here we show that these combinatorial circuits integrated a two-molecule input and performed digital computations with NOT, AND, NAND and N-IMPLY expression logic in single mammalian cells. Functional interconnection of two N-IMPLY variants resulted in bitwise intracellular XOR operations, and a combinatorial arrangement of three logic gates enabled independent cells to perform programmable half-subtractor and half-adder calculations. Individual mammalian cells capable of executing basic molecular arithmetic functions isolated or coordinated to metabolic activities in a predictable, precise and robust manner may provide new treatment strategies and bio-electronic interfaces in future gene-based and cell-based therapies.

Quorum sensing is a promising target for next-generation anti-infectives designed to address evolving bacterial drug resistance. The autoinducer-2 (AI-2) is a key quorum-sensing signal molecule which regulates bacterial group behaviors and is recognized by many Gram-negative and Gram-positive bacteria. Here we report a synthetic mammalian cell-based microbial-control device that detects microbial chemotactic formyl peptides through a formyl peptide sensor (FPS) and responds by releasing AI-2. The microbial-control device was designed by rewiring an artificial receptor-based signaling cascade to a modular biosynthetic AI-2 production platform. Mammalian cells equipped with the microbial-control gene circuit detect formyl peptides secreted from various microbes with high sensitivity and respond with robust AI-2 production, resulting in control of quorum sensing-related behavior of pathogenic Vibrio harveyi and attenuation of biofilm formation by the human pathogen Candida albicans . The ability to manipulate mixed microbial populations through fine-tuning of AI-2 levels may provide opportunities for future anti-infective strategies. Bacterial populations communicate with AI-2 signaling molecules, helping to coordinate biofilm development and other group behaviors. Here the authors design a genetic circuit for mammalian cells that allows them to sense bacterial populations and interfere with quorum communication.

PurposeIndustry 4.0 is assumed to yield extensive industry-spanning opportunities. However, exploiting these opportunities requires a targeted implementation of Industry 4.0. The purpose of this paper is to generate a deeper understanding of relevant implementation action. Existing recommendations are mostly general, highly aggregated and difficult to grasp. Yet, specific and concrete actions that need to be taken to accelerate the realization of Industry 4.0 are essential.Design/methodology/approachThe article uses 13 semi-structured in-depth expert interviews as the source of empirical data. The interviews were conducted with managers from Industry 4.0-experienced German manufacturing companies. All interviews are analyzed using qualitative content analysis.FindingsThe study reveals relevant and targeted aspects for Industry 4.0 implementation: the development of Industry 4.0-specific know-how, securing financial resources, integrating employees into the implementation process and establishing an open-minded and flexible corporate culture. Further aspects include comprehensive planning processes, cooperation with external partners, proper handling of data interfaces, interdisciplinary communication, an adaptable organizational structure and data security.Research limitations/implicationsThe paper is limited to German manufacturing enterprises and should be transferred to other industries and countries.Practical implicationsThe study supports managers to effectively implement Industry 4.0 within their organizations and consequently benefit from Industry 4.0 and derives recommendations for future research.Originality/valueThe paper is among the first to give specific and concrete examples for lessons learned from Industry 4.0 implementation, directly obtained from industrial application.

In this paper we consider an obstacle problem for a generalization of the p -elastic energy among graphical curves with fixed ends. Taking into account that the Euler–Lagrange equation has a degeneracy, we address the question whether solutions have a flat part, i.e. an open interval where the curvature vanishes. We also investigate which is the main cause of the loss of regularity, the obstacle or the degeneracy. Moreover, we give several conditions on the obstacle that assure existence and nonexistence of solutions. The analysis can be refined in the special case of the p -elastica functional, where we obtain sharp existence results and uniqueness for symmetric minimizers.

The sediment record of coccoliths dates back to the Late Triassic (Bown et al., 2004), and the geochemical composition of coccoliths offers a potential paleoproxy to reconstruct past environmental conditions (Hermoso, 2014; McClelland et al., 2017; Müller et al., 2018). Since the discovery that coccoliths are of biological origin (Sorby, 1861), the general understanding of coccolithophore calcification has substantially increased and the underlying calcium carbonate precipitation kinetics and the cellular mechanisms involved have been partly revealed (e.g., Mackinder et al., 2011; Mejía et al., 2018). [...]the explanation that calcification evolved initially as a protective function or to reduce grazing pressure seems to be goal directed or teleological. [...]we need to consider the possibility that the historical genesis of calcification in coccolithophores served a quite different function and benefits compared to modern ecological settings. First experimental evidence suggests that the ability to calcify provides an efficient mechanism for intracellular Ca2+ detoxification which would be of advantage at geological times of elevated seawater Ca2+ concentrations (e.g., Cretaceous and Jurassic) in comparison to the relatively low modern oceanic concentration (Müller et al., 2015).