Orientation and Search Strategies of Desert Arthropods : Path Integration Models and Experiments with Desert Ants, <i>Cataglyphis fortis</i> (Forel 1902)

Path integration enables desert arthropods to find back to their nest on the shortest track from any position. To perform path integration successfully, speeds and turning angles along the preceding outbound path have to be measured continuously and combined to determine an internal global vector leading back home at any time. A number of experiments have given an idea how arthropods might use allothetic or idiothetic signals to perceive their orientation and moving speed. When the global vector has been run off but the nest has not yet been reached, the arthropods engage in systematic search behavior. This behavior consists of a series of search loops of ever increasing size and finally leads to a search density profile peaking at the starting location. In the theoretical part of this work, the model descriptions of mathematically precise path integration that have been developed so far are reviewed, and the hitherto not used variant of egocentric cartesian coordinates is proposed and explained. Its simple and intuitive structure is demonstrated in comparison to the previous path integration models. Measuring two quantities, forward moving speed and angular turning rate, and implementing them into a linear system of differential equations provides the necessary information during foraging run, reorientation process (e.g. at a feeding site) and return path to the nest. In addition, several possible types of systematic errors that can cause deviations from the correct homeward course are easily implemented and illustrated by means of the model. Such deviations have been observed for several species of desert arthropods in different experiments, but their origin is still under debate. The two most important error mechanisms in this respect are the Müller-Wehner-error, an approximative path integration model that accumulates systematic miscalculations in path integration whenever the animal walks different from the correct inbound and outbound direction, and the leaky integrator, a mechanism that predicts a linear underestimation of the distance to the nest with an exponential rate; both error types have been shown to occur in specific experimental paradigms with desert ants Cataglyphis fortis. Using the egocentric path integration model, simple indices are proposed that might allow to rule out or corroborate certain error types by conducting experiments. Experiments were conducted with desert ants C. fortis. Those experiments, in which natural outbound runs as well as the following inbound runs and systematic search behaviors were observed and analyzed, revealed that natural outbound runs do not differ remarkably among different ants. This holds true for their spatial conformation as well as for overall path length and distance covered during foraging. Consequently, no significant correlations between all factors determining the shape of the outbound runs and the errors that were measured via different variables for inbound run as well as systematic search were found. Besides, the extension of the systematic search does not differ remarkably. However, due to the only slight differences of the natural outbound runs, such correlations cannot be totally excluded. The error postulated by Müller and Wehner seems to be of no or minor importance during natural foraging excursions; the principle of the leaky integrator, on the other hand, might be able to explain some shortcomings of the path integration mechanism with respect to distance estimation. Repeated training increases the straightness of outbound runs. In experiments, where desert ants were trained to different distances, it became obvious that the longer the distances of foraging excursions, the larger the errors occurring during path integration (again measured via home run and systematic search), and that the ants adapt their systematic search strategy to their increasing uncertainty by extending the search pattern. Additional experiments, during which the distance was kept constant, revealed that not only the characteristics of the foraging trip influence the accuracy of path integrator and systematic search behavior, but that also nest- or route specific cues have an impact on the orientation and the systematic search patterns of desert ants. If desert ants are disturbed during their outbound runs, most of them immediately set out in direction back to the nest, even without having food in their mandibles. External cues, in the respective experiment huge landmarks placed on the route between nest and feeder, increased the number of ants that continued its preceding foraging run; but still the majority headed back towards the nest. For a number of ants successive outbound and inbound runs (ontogeny-experiment) were recorded and analyzed. As a result, their outbound runs to a known feeding site get straighter over time, whereas the inbound runs are very straight from the very beginning and no increase of their straightness could be observed. For both outbound and inbound runs also no improvement in terms of accuracy of the path integrator was found; obviously the ants perform path integration in the same fashion all the time. Even if trained to a feeder for a long time in an area free of landmarks, desert ants do not develop specific paths, as they have been observed for other species of desert arthropods

A Particle-based Multiscale Solver for Compressible Liquid-Vapor Flow

To describe complex flow systems accurately, it is in many cases important to account for the properties of fluid flows on a microscopic scale. In this work, we focus on the description of liquid-vapor flow with a sharp interface between the phases. The local phase dynamics at the interface can be interpreted as a Riemann problem for which we develop a multiscale solver in the spirit of the heterogeneous multiscale method, using a particle-based microscale model to augment the macroscopic two-phase flow system. The application of a microscale model makes it possible to use the intrinsic properties of the fluid at the microscale, instead of formulating (ad-hoc) constitutive relations

Black Boxes - Versiegelungskontexte und Öffnungsversuche – Interdisziplinäre Perspektiven

Wir sind von komplexen Dingen umgeben, die gleichzeitig wirken und doch hinter Interfaces verborgen sind. Dies gilt für die Datennetze, in denen wir uns bewegen, genauso wie für autonome Systeme, die unsere Daten verarbeiten. SmartWatches, Künstliche Intelligenz oder CRISPR-Cas9 sind rezente Beispiele für solche Black Boxes, der Buchdruck oder schon früheste Steinwerkzeuge historische. In dem vorliegenden interdisziplinären Band werden Versiegelungskontexte dieser Black Boxes untersucht oder Öffnungsversuche dieser dargestellt. Im Mittelpunkt der Untersuchungen stehen einzelne Fallbeispiele anhand derer theoretische Untersuchungswerkzeuge erprobt werden. Theorieimpulse kommen hierbei aus den Science and Technology Studies und der Medienwissenschaft, sind angeregt durch den Material Culture Turn, aber auch von einer (digitalen) Phänomenologie und Hermeneutik. Dreizehn Beiträge in vier Abschnitten kartieren beispielhaft das Feld; eingebettet und abgerundet werden diese durch vier Respondenzen und einen ergänzenden Beitrag zur Ideengeschichte der Automaten. Der Band liefert somit einen Überblick über aktuelle Technikforschung in Deutschland anhand des Beispiels der Black Box, die jedoch in der Geschichte der Diskussion geerdet wird

Modeling plasticity and dysplasia of pancreatic ductal organoids derived from human pluripotent stem cells

Personalized in vitro models for dysplasia and carcinogenesis in the pancreas have been constrained by insufficient differentiation of human pluripotent stem cells (hPSCs) into the exocrine pancreatic lineage. Here, we differentiate hPSCs into pancreatic duct-like organoids (PDLOs) with morphological, transcriptional, proteomic, and functional characteristics of human pancreatic ducts, further maturing upon transplantation into mice. PDLOs are generated from hPSCs inducibly expressing oncogenic GNAS, KRAS, or KRAS with genetic covariance of lost CDKN2A and from induced hPSCs derived from a McCune-Albright patient. Each oncogene causes a specific growth, structural, and molecular phenotype in vitro. While transplanted PDLOs with oncogenic KRAS alone form heterogenous dysplastic lesions or cancer, KRAS with CDKN2A loss develop dedifferentiated pancreatic ductal adenocarcinomas. In contrast, transplanted PDLOs with mutant GNAS lead to intraductal papillary mucinous neoplasia-like structures. Conclusively, PDLOs enable in vitro and in vivo studies of pancreatic plasticity, dysplasia, and cancer formation from a genetically defined background

Operating performance of full-scale agricultural biogas plants in Germany and China : results of a year-round monitoring program

Germany (DE) and China (CN) have different political approaches in supporting the biogas sector. Three German and three Chinese large-scale biogas plants (BGPs) were evaluated as part of a year-round monitoring program. Laboratory methods were utilized to analyze the chemical indicators. Results showed a stable anaerobic digestion process without system failures in all BGPs. The methane yield had a range of 0.23–0.35 m3 CH4/kgODM for DE BGPs and 0.11–0.22 m3 CH4/kgODM for CN BGPs, due to different substrates and working temperatures. Financial analyses indicated that DE BGPs are viable under their current feed-in tariffs contracts. Their financial internal rate of return (IRR) ranged between 8 and 22%. However, all CN BGPs had negative IRRs, indicating that they are financially unfeasible. Risk analyses illustrated that DE BGPs will face financial nonviability if benefits decrease by 9–33% or costs increase by 10–49%, or if a combined worse case (benefit decrease and cost increase) of 5 20% occurs. Incentives to BGP operations are particularly important in China, where the government should consider switching the construction-based subsidy to a performancebased subsidy system to motivate the operators. BGP monitoring is necessary to understand the performance, in addition to briefing policymakers in case a policy reform is neede

Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium

Double-stranded DNA (dsDNA) constitutes a potent activator of innate immunity, given its ability to bind intracellular pattern recognition receptors during viral infections or sterile tissue damage. While effects of dsDNA in immune cells have been extensively studied, dsDNA signalling and its pathophysiological implications in non-immune cells, such as the vascular endothelium, remain poorly understood. The aim of this study was to characterize prothrombotic effects of dsDNA in vascular endothelial cells. Transfection of cultured human endothelial cells with the synthetic dsDNA poly(dA:dT) induced upregulation of the prothrombotic molecules tissue factor and PAI-1, resulting in accelerated blood clotting in vitro, which was partly dependent on RIG-I signalling. Prothrombotic effects were also observed upon transfection of endothelial cells with hepatitis B virus DNA-containing immunoprecipitates as well human genomic DNA. In addition, dsDNA led to surface expression of von Willebrand factor resulting in increased platelet-endothelium-interactions under flow. Eventually, intrascrotal injection of dsDNA resulted in accelerated thrombus formation upon light/dye-induced endothelial injury in mouse cremaster arterioles and venules in vivo. In conclusion, we show that viral or endogenous dsDNA induces a prothrombotic phenotype in the vascular endothelium. These findings represent a novel link between pathogen-and danger-associated patterns within innate immunity and thrombosis

Clinical response after two cycles compared to HER2, Ki-67, p53, and bcl-2 in independently predicting a pathological complete response after preoperative chemotherapy in patients with operable carcinoma of the breast

Introduction To investigate the predictive value of clinical and biological markers for a pathological complete remission after a preoperative dose-dense regimen of doxorubicin and docetaxel, with or without tamoxifen, in primary operable breast cancer. Methods Patients with a histologically confirmed diagnosis of previously untreated, operable, and measurable primary breast cancer (tumour (T), nodes (N) and metastases (M) score: T2-3(>= 3 cm) N0-2 M0) were treated in a prospectively randomised trial with four cycles of dose-dense (bi-weekly) doxorubicin and docetaxel (ddAT) chemotherapy, with or without tamoxifen, prior to surgery. Clinical and pathological parameters (menopausal status, clinical tumour size and nodal status, grade, and clinical response after two cycles) and a panel of biomarkers (oestrogen and progesterone receptors, Ki-67, human epidermal growth factor receptor 2 (HER2), p53, bcl-2, all detected by immunohistochemistry) were correlated with the detection of a pathological complete response (pCR). Results A pCR was observed in 9.7% in 248 patients randomised in the study and in 8.6% in the subset of 196 patients with available tumour tissue. Clinically negative axillary lymph nodes, poor tumour differentiation, negative oestrogen receptor status, negative progesterone receptor status, and loss of bcl-2 were significantly predictive for a pCR in a univariate logistic regression model, whereas in a multivariate analysis only the clinical nodal status and hormonal receptor status provided significantly independent information. Backward stepwise logistic regression revealed a response after two cycles, with hormone receptor status and lymph-node status as significant predictors. Patients with a low percentage of cells stained positive for Ki-67 showed a better response when treated with tamoxifen, whereas patients with a high percentage of Ki-67 positive cells did not have an additional benefit when treated with tamoxifen. Tumours overexpressing HER2 showed a similar response to that in HER2-negative patients when treated without tamoxifen, but when HER2-positive tumours were treated with tamoxifen, no pCR was observed. Conclusion Reliable prediction of a pathological complete response after preoperative chemotherapy is not possible with clinical and biological factors routinely determined before start of treatment. The response after two cycles of chemotherapy is a strong but dependent predictor. The only independent factor in this subset of patients was bcl-2. Trial registration number NCT0054382

A Distributed and Trusted Web of Formal Proofs

International audienceMost computer checked proofs are tied to the particular technology of a prover's software. While sharing results between proof assistants is a recognized and desirable goal, the current organization of theorem proving tools makes such sharing an exception instead of the rule. In this talk, I argue that we need to turn the current architecture of proof assistants and formal proofs inside-out. That is, instead of having a few mature theorem provers include within them their formally checked theorems and proofs, I propose that proof assistants should sit on the edge of a web of formal proofs and that proof assistant should be exporting their proofs so that they can exist independently of any theorem prover. While it is necessary to maintain the dependencies between definitions, theories, and theorems, no explicit library structure should be imposed on this web of formal proofs. Thus a theorem and its proofs should not necessarily be located at a particular URL or within a particular prover's library. While the world of symbolic logic and proof theory certainly allows for proofs to be seen as global and permanent objects, there is a lot of research and engineering work that is needed to make this possible. I describe some of the required research and development that must be done to achieve this goal

Harnessing the Potential of Human Pluripotent Stem Cells and Gene Editing for the Treatment of Retinal Degeneration

PURPOSE OF REVIEW: A major cause of visual disorders is dysfunction and/or loss of the light-sensitive cells of the retina, the photoreceptors. To develop better treatments for patients, we need to understand how inherited retinal disease mutations result in the dysfunction of photoreceptors. New advances in the field of stem cell and gene editing research offer novel ways to model retinal dystrophies in vitro and present opportunities to translate basic biological insights into therapies. This brief review will discuss some of the issues that should be taken into account when carrying out disease modelling and gene editing of retinal cells. We will discuss (i) the use of human induced pluripotent stem cells (iPSCs) for disease modelling and cell therapy; (ii) the importance of using isogenic iPSC lines as controls; (iii) CRISPR/Cas9 gene editing of iPSCs; and (iv) in vivo gene editing using AAV vectors.RECENT FINDINGS: Ground-breaking advances in differentiation of iPSCs into retinal organoids and methods to derive mature light sensitive photoreceptors from iPSCs. Furthermore, single AAV systems for in vivo gene editing have been developed which makes retinal in vivo gene editing therapy a real prospect.SUMMARY: Genome editing is becoming a valuable tool for disease modelling and in vivo gene editing in the retina.</p