A mesocosm experiment investigating the effects of substratum quality and wave exposure on the survival of fish eggs

In a mesocosm experiment, the attachment of bream (Abramis brama) eggs to spawning substrata with and without periphytic biofilm coverage and their subsequent survival with and without low-intensity wave exposure were investigated. Egg attachment was reduced by 73% on spawning substrata with a natural periphytic biofilm, compared to clean substrata. Overall, this initial difference in egg numbers persisted until hatching. The difference in egg numbers was even increased in the wave treatment, while it was reduced in the no-wave control treatment. Exposure to a low-intensity wave regime affected egg development between the two biofilm treatments differently. Waves enhanced egg survival on substrata without a biofilm but reduced the survival of eggs on substrata with biofilm coverage. In the treatment combining biofilm-covered substrata and waves, no attached eggs survived until hatching. In all treatments, more than 75% of the eggs became detached from the spawning substrata during the egg incubation period, an

Validation of Stochastic Optimal Control Models for Goal-Directed Human Movements on the Example of Human Driving Behavior

Stochastic Optimal Control models represent the state-of-the-art in modeling goal-directed human movements. The linear-quadratic sensorimotor (LQS) model based on signal-dependent noise processes in state and output equation is the current main representative. With our newly introduced Inverse Stochastic Optimal Control algorithm building upon two bi-level optimizations, we can identify its unknown model parameters, namely cost function matrices and scaling parameters of the noise processes, for the first time. In this paper, we use this algorithm to identify the parameters of a deterministic linear-quadratic, a linear-quadratic Gaussian and a LQS model from human measurement data to compare the models' capability in describing goal-directed human movements. Human steering behavior in a simplified driving task shown to posses similar features as point-ot-point human hand reaching movements serves as our example movement. The results show that the identified LQS model outperforms the others with statistical significance. Particularly, the average human steering behavior is modeled significantly better by the LQS model. This validates the positive impact of signal-dependent noise processes on modeling human average behavior

Unique coding for authentication and anti-counterfeiting by controlled and random process variation in L-PBF and L-DED

Additive manufacturing technologies enable various possibilities to create and modify the material composition and structure on a local level, but are often prone to undesired defects and inhomogeneities. This contribution makes use of such flaws to generate material-inherent, hidden codes and watermarks in metals for authentication and anti-counterfeiting applications. By controlled and random process variation, unique codes that can be read and authenticated by an eddy current device were produced with the processes of laser powder bed fusion (L-PBF) and laser directed energy deposition (L-DED). Two approaches are presented: First, volumetric, porous structures with a defined shape are manufactured with L-PBF. Second, coatings are fabricated by L-DED with alternating process parameters, leading to local deviations of the magnetic permeability. This non-deterministic coding approach generates a distinctive material structure that triggers high signal amplitudes in the eddy current measurement. Counterfeiting becomes impossible due to the irreproducible melt pool dynamics. Statistical hypothesis testing proves that the system is able to prevent false acceptance or rejection of a code with a certainty of 500 million to one. A low-cost setup for a novel locking system demonstrates that a code can be sensed reliably within one second

Ground verification of the feasibility of telepresent on-orbit servicing

In an ideal case telepresence achieves a state in which a human operator can no longer differentiate between an interaction with a real environment and a technical mediated one. This state is called transparent telepresence. The applicability of telepresence to on-orbit servicing (OOS), i.e., an unmanned servicing operation in space, teleoperated from ground in real time, is verified in this paper. For this purpose, a communication test environment was set up on the ground, which involved the Institute of Astronautics (LRT) ground station in Garching, Germany, and the European Space Agency (ESA) ground station in Redu, Belgium. Both were connected via the geostationary ESA data relay satellite ARTEMIS. Utilizing the data relay satellite, a teleoperation was accomplished in which the human operator as well as the (space) teleoperator was located on the ground. The feasibility of telepresent OOS was evaluated, using an OOS test bed at the Institute of Mechatronics and Robotics at the German Aerospace Center (DLR). The manipulation task was representative for OOS and supported real-time feedback from the haptic-visual workspace. The tests showed that complex manipulation tasks can be fulfilled by utilizing geostationary data relay satellites. For verifying the feasibility of telepresent OOS, different evaluation methods were used. The properties of the space link were measured and related to subjective perceptions of participants, who had to fulfill manipulation tasks. An evaluation of the transparency of the system, including the data relay satellite, was accomplished as well

Calculation of Wave-functions with Frozen Orbitals in Mixed Quantum Mechanics/Molecular Mechanics methods. I. Application of the Huzinaga Equation.

Mixed quantum mechanics/quantum mechanics (QM/QM) and quantum mechan- ics/molecular mechanics (QM/MM) methods make computations feasible for extended chemical systems by separating them into subsystems that are treated at different level of sophistication. In many applications the subsystems are covalently bound and the use of frozen localized orbitals at the boundary is a possible way to separate the sub- systems and to ensure a sensible description of the electronic structure near to the boundary. A complication in these methods is that orthogonality between optimized and frozen orbitals has to be warranted and this is usually achieved by an explicit or- thogonalization of the basis set to the frozen orbitals. An alternative to this approach is proposed by calculating the wave-function from the Huzinaga-equation that guaranties orthogonality to the frozen orbitals without basis set orthogonalization. The theoreti- cal background and the practical aspects of the application of the Huzinaga equation in mixed methods is discussed. Forces have been derived to perform geometry opti- mization with wave-functions from the Huzinaga-equation. Various properties have been calculated applying the Huzinaga-equation for the central QM subsystem, repre- senting the environment by point charges and using frozen strictly localized orbitals to connect the subsystems. It is shown that a 2-3 bond separation of the chemical or physical event from the frozen bonds allows a very good reproduction (typically around 1 kcal/mol) of standard Hartree-Fock-Roothaan results. The proposed scheme provides an appropriate framework for mixed QM/QM and QM/MM methods

2-Year Outcomes of High Bleeding Risk Patients After Polymer-Free Drug-Coated Stents.

BACKGROUND: A 1-year follow-up, polymer-free metallic stent coated with biolimus-A9 followed by 1-month dual antiplatelet therapy is safer and more effective than a bare-metal stent (BMS) for patients with high risk of bleeding. OBJECTIVES: This study analyzed 2-year outcomes to determine whether these benefits are maintained. METHODS: In a prospective, multicenter, double-blind trial, we randomized 2,466 high bleeding risk patients to receive a drug-coated stent (DCS) or a BMS followed by 1-month dual antiplatelet therapy. The primary safety endpoint was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy endpoint was clinically driven target lesion revascularization. RESULTS: At 2 years, the primary safety endpoint had occurred in 147 DCS and 180 BMS patients (15.3%) (hazard ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.039). Clinically driven target lesion revascularization occurred for 77 DCS and 136 BMS patients (12.0%) (hazard ratio: 0.54; 95% confidence interval: 0.41 to 0.72; p 75 years, anemia, raised plasma creatinine, and planned long-term anticoagulation. Correlates of the primary safety endpoint were age, anemia, congestive heart failure, multivessel disease, number of stents implanted, and use of a BMS rather than a DCS. CONCLUSIONS: Safety and efficacy benefits of DCS over BMS were maintained for 2 years in high bleeding risk patients. Rates of major bleeding and coronary thrombotic events were no different and were associated with a substantial and comparable mortality risk. (A Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug Coated Stent Versus the Gazelle Bare Metal Stent in Patients With High Risk of Bleeding [LEADERS FREE]; NCT01623180)

Activated Platelets in Carotid Artery Thrombosis in Mice Can Be Selectively Targeted with a Radiolabeled Single-Chain Antibody

BACKGROUND: Activated platelets can be found on the surface of inflamed, rupture-prone and ruptured plaques as well as in intravascular thrombosis. They are key players in thrombosis and atherosclerosis. In this study we describe the construction of a radiolabeled single-chain antibody targeting the LIBS-epitope of activated platelets to selectively depict platelet activation and wall-adherent non-occlusive thrombosis in a mouse model with nuclear imaging using in vitro and ex vivo autoradiography as well as small animal SPECT-CT for in vivo analysis. METHODOLOGY/PRINCIPAL FINDINGS: LIBS as well as an unspecific control single-chain antibody were labeled with (111)Indium ((111)In) via bifunctional DTPA ( = (111)In-LIBS/(111)In-control). Autoradiography after incubation with (111)In-LIBS on activated platelets in vitro (mean 3866 ± 28 DLU/mm(2), 4010 ± 630 DLU/mm(2) and 4520 ± 293 DLU/mm(2)) produced a significantly higher ligand uptake compared to (111)In-control (2101 ± 76 DLU/mm(2), 1181 ± 96 DLU/mm(2) and 1866 ± 246 DLU/mm(2)) indicating a specific binding to activated platelets; P<0.05. Applying these findings to an ex vivo mouse model of carotid artery thrombosis revealed a significant increase in ligand uptake after injection of (111)In-LIBS in the presence of small thrombi compared to the non-injured side, as confirmed by histology (49630 ± 10650 DLU/mm(2) vs. 17390 ± 7470 DLU/mm(2); P<0.05). These findings could also be reproduced in vivo. SPECT-CT analysis of the injured carotid artery with (111)In-LIBS resulted in a significant increase of the target-to-background ratio compared to (111)In-control (1.99 ± 0.36 vs. 1.1 ± 0.24; P < 0.01). CONCLUSIONS/SIGNIFICANCE: Nuclear imaging with (111)In-LIBS allows the detection of platelet activation in vitro and ex vivo with high sensitivity. Using SPECT-CT, wall-adherent activated platelets in carotid arteries could be depicted in vivo. These results encourage further studies elucidating the role of activated platelets in plaque pathology and atherosclerosis and might be of interest for further developments towards clinical application

Genomic changes associated with the evolutionary transition of an insect gut symbiont into a blood-borne pathogen.

The genus Bartonella comprises facultative intracellular bacteria with a unique lifestyle. After transmission by blood-sucking arthropods they colonize the erythrocytes of mammalian hosts causing acute and chronic infectious diseases. Although the pathogen-host interaction is well understood, little is known about the evolutionary origin of the infection strategy manifested by Bartonella species. Here we analyzed six genomes of Bartonella apis, a honey bee gut symbiont that to date represents the closest relative of pathogenic Bartonella species. Comparative genomics revealed that B. apis encodes a large set of vertically inherited genes for amino acid and cofactor biosynthesis and nitrogen metabolism. Most pathogenic bartonellae have lost these ancestral functions, but acquired specific virulence factors and expanded a vertically inherited gene family for harvesting cofactors from the blood. However, the deeply rooted pathogen Bartonella tamiae has retained many of the ancestral genome characteristics reflecting an evolutionary intermediate state toward a host-restricted intraerythrocytic lifestyle. Our findings suggest that the ancestor of the pathogen Bartonella was a gut symbiont of insects and that the adaptation to blood-feeding insects facilitated colonization of the mammalian bloodstream. This study highlights the importance of comparative genomics among pathogens and non-pathogenic relatives to understand disease emergence within an evolutionary-ecological framework

IL-33-induced metabolic reprogramming controls the differentiation of alternatively activated macrophages and the resolution of inflammation

Alternatively activated macrophages (AAMs) contribute to the resolution of inflammation and tissue repair. However, molecular pathways that govern their differentiation have remained incompletely understood. Here, we show that uncoupling protein-2-mediated mitochondrial reprogramming and the transcription factor GATA3 specifically controlled the differentiation of pro-resolving AAMs in response to the alarmin IL-33. In macrophages, IL-33 sequentially triggered early expression of pro-inflammatory genes and subsequent differentiation into AAMs. Global analysis of underlying signaling events revealed that IL-33 induced a rapid metabolic rewiring of macrophages that involved uncoupling of the respiratory chain and increased production of the metabolite itaconate, which subsequently triggered a GATA3-mediated AAM polarization. Conditional deletion of GATA3 in mononuclear phagocytes accordingly abrogated IL-33-induced differentiation of AAMs and tissue repair upon muscle injury. Our data thus identify an IL-4-independent and GATA3-dependent pathway in mononuclear phagocytes that results from mitochondrial rewiring and controls macrophage plasticity and the resolution of inflammation