Showing papers by "Fraunhofer Society published in 2016"

Cyber-physical systems in manufacturing

Abstract: One of the most significant advances in the development of computer science, information and communication technologies is represented by the cyber-physical systems (CPS). They are systems of collaborating computational entities which are in intensive connection with the surrounding physical world and its on-going processes, providing and using, at the same time, data-accessing and data-processing services available on the Internet. Cyber-physical production systems (CPPS), relying on the latest, and the foreseeable further developments of computer science, information and communication technologies on one hand, and of manufacturing science and technology, on the other, may lead to the 4th industrial revolution, frequently noted as Industrie 4.0. The paper underlines that there are significant roots in general – and in particular to the CIRP community – which point towards CPPS. Expectations towards research in and implementation of CPS and CPPS are outlined and some case studies are introduced. Related new R&D challenges are highlighted.

Early dissemination seeds metastasis in breast cancer

Abstract: Accumulating data suggest that metastatic dissemination often occurs early during tumour formation, but the mechanisms of early metastatic spread have not yet been addressed. Here, by studying metastasis in a HER2-driven mouse breast cancer model, we show that progesterone-induced signalling triggers migration of cancer cells from early lesions shortly after HER2 activation, but promotes proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by increased HER2 expression and tumour-cell density involving microRNA-mediated progesterone receptor downregulation, and was reversible. Cells from early, low-density lesions displayed more stemness features, migrated more and founded more metastases than cells from dense, advanced tumours. Notably, we found that at least 80% of metastases were derived from early disseminated cancer cells. Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination.

A brain–spine interface alleviating gait deficits after spinal cord injury in primates

Abstract: Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

Mechanism of early dissemination and metastasis in Her2 + mammary cancer

Abstract: Metastasis is the leading cause of cancer-related deaths; metastatic lesions develop from disseminated cancer cells (DCCs) that can remain dormant. Metastasis-initiating cells are thought to originate from a subpopulation present in progressed, invasive tumours. However, DCCs detected in patients before the manifestation of breast-cancer metastasis contain fewer genetic abnormalities than primary tumours or than DCCs from patients with metastases. These findings, and those in pancreatic cancer and melanoma models, indicate that dissemination might occur during the early stages of tumour evolution. However, the mechanisms that might allow early disseminated cancer cells (eDCCs) to complete all steps of metastasis are unknown. Here we show that, in early lesions in mice and before any apparent primary tumour masses are detected, there is a sub-population of Her2+p-p38lop-Atf2loTwist1hiE-cadlo early cancer cells that is invasive and can spread to target organs. Intra-vital imaging and organoid studies of early lesions showed that Her2+ eDCC precursors invaded locally, intravasated and lodged in target organs. Her2+ eDCCs activated a Wnt-dependent epithelial-mesenchymal transition (EMT)-like dissemination program but without complete loss of the epithelial phenotype, which was reversed by Her2 or Wnt inhibition. Notably, although the majority of eDCCs were Twist1hiE-cadlo and dormant, they eventually initiated metastasis. Our work identifies a mechanism for early dissemination in which Her2 aberrantly activates a program similar to mammary ductal branching that generates eDCCs that are capable of forming metastasis after a dormancy phase.

Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial

Abstract: Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 × 106 cells), medium dose (10 × 106), and high dose (50 × 106). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy. Significance Although this phase I study included a limited number of patients without a placebo arm, it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis. This study also provides encouraging preliminary evidence of efficacy. Larger and controlled long-term studies are now mandatory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis.

Cryogenic manufacturing processes

Abstract: Cryogenically assisted manufacturing processes are emerging as environmentally-benign, toxic-free, hazardless operations, producing functionally superior products. This paper presents an overview of major cryogenic manufacturing processes, summarizing the state-of-the-art and significant developments during the last few decades. It begins with a summary of historic perspectives, including definitions, scope, and proceeds to analysis of process mechanics and material performance covering tribological and thermo-mechanical interactions, followed by surface integrity, product quality and performance in cryogenic manufacturing. Process analysis and applications includes machining, forming and grinding. Economic, safety and health issues are then discussed. Finally, progress in developing predictive performance models and future outlook are presented.

Tailored Buckling Microlattices as Reusable Light‐Weight Shock Absorbers

Abstract: Structures and materials absorbing mechanical (shock) energy commonly exploit either viscoelasticity or destructive modifications. Based on a class of uniaxial light-weight geometrically nonlinear mechanical microlattices and using buckling of inner elements, either a sequence of snap-ins followed by irreversible hysteretic - yet repeatable - self-recovery or multistability is achieved, enabling programmable behavior. Proof-of-principle experiments on three-dimensional polymer microstructures are presented.

Health Benefits of Anthocyanins and Their Encapsulation for Potential Use in Food Systems: A Review

Abstract: Anthocyanins are one of the six subgroups of large and widespread group of plant constituents known as flavonoids. These are responsible for the bright and attractive orange, red, purple, and blue colors of most fruits, vegetables, flowers and some cereal grains. More than 600 structurally distinct anthocyanins have been identified in nature. Earlier, anthocyanins were only known for their coloring properties but now interest in anthocyanin pigments has intensified because of their possible health benefits as dietary antioxidants, which help to prevent neuronal diseases, cardiovascular illnesses, cancer, diabetes, inflammation, and many such others diseases. Ability of anthocyanins to counter oxidants makes them atherosclerosis fighters. Therefore, anthocyanin-rich foods may help to boost overall health by offering an array of nutrients. However, the incorporation of anthocyanins into food and medical products is a challenging task due to their low stability toward environmental conditions during processing and storage. Encapsulation seems to be an efficient way to introduce such compounds into these products. Encapsulating agents act as a protector coat against ambient adverse conditions such as light, humidity, and oxygen. Encapsulated bioactive compounds are easier to handle and offer improved stability. The main objective of this review is to explore health benefits of anthocyanins and their extraction, characterization, encapsulation, and delivery.

Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury

Abstract: Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans.

UV Degradation and Recovery of Perovskite Solar Cells

Abstract: Although the power conversion efficiency of perovskite solar cells has increased from 3.81% to 22.1% in just 7 years, they still suffer from stability issues, as they degrade upon exposure to moisture, UV light, heat, and bias voltage. We herein examined the degradation of perovskite solar cells in the presence of UV light alone. The cells were exposed to 365 nm UV light for over 1,000 h under inert gas at <0.5 ppm humidity without encapsulation. 1-sun illumination after UV degradation resulted in recovery of the fill factor and power conversion efficiency. Furthermore, during exposure to consecutive UV light, the diminished short circuit current density (Jsc) and EQE continuously restored. 1-sun light soaking induced recovery is considered to be caused by resolving of stacked charges and defect state neutralization. The Jsc and EQE bounce-back phenomenon is attributed to the beneficial effects of PbI2 which is generated by the decomposition of perovskite material.

Four-Junction Wafer-Bonded Concentrator Solar Cells

Abstract: The highest solar cell conversion efficiencies are achieved with four-junction devices under concentrated sunlight illumination. Different cell architectures are under development, all targeting an ideal bandgap combination close to 1.9, 1.4, 1.0, and 0.7 eV. Wafer bonding is used in this work to combine materials with a significant lattice mismatch. Three cell architectures are presented using the same two top junctions of GaInP/GaAs but different infrared absorbers based on Germanium, GaSb, or GaInAs on InP. The modeled efficiency potential at 500 suns is in the range of 49–54% for all three devices, but the highest efficiency is expected for the InP-based cell. An efficiency of 46% at 508 suns was already measured by AIST in Japan for a GaInP/GaAs//GaInAsP/GaInAs solar cell and represents the highest independently confirmed efficiency today. Solar cells on Ge and GaSb are in the development phase at Fraunhofer ISE, and the first demonstration of functional devices is presented in this paper.

Effect of surface roughness on fatigue performance of additive manufactured Ti–6Al–4V

Abstract: Additive manufacturing is increasingly considered for production of high quality, metallic, aerospace parts. Despite the high potential of this manufacturing process to reduce weight and lead time, the fundamental understanding of additive manufactured Ti–6Al–4V material is still at an early stage, especially in the area of fatigue and damage tolerance. This paper covers the effects of inherent surface roughness on the fatigue life. In the as built condition, metallic parts have a poor surface texture, which is generally removed in fatigue critical areas. It is shown that the fatigue properties of Ti–6Al–4V samples, produced by direct metal laser sintering and electron beam melting, are dominated by surface roughness effects. A simple model based on an equivalent initial flaw size is formulated.

The 2016 Thermal Spray Roadmap

Abstract: Considerable progress has been made over the last decades in thermal spray technologies, practices and applications. However, like other technologies, they have to continuously evolve to meet new problems and market requirements. This article aims to identify the current challenges limiting the evolution of these technologies and to propose research directions and priorities to meet these challenges. It was prepared on the basis of a collection of short articles written by experts in thermal spray who were asked to present a snapshot of the current state of their specific field, give their views on current challenges faced by the field and provide some guidance as to the R&D required to meet these challenges. The article is divided in three sections that deal with the emerging thermal spray processes, coating properties and function, and biomedical, electronic, aerospace and energy generation applications.

Band structure engineering in organic semiconductors

Abstract: A key breakthrough in modern electronics was the introduction of band structure engineering, the design of almost arbitrary electronic potential structures by alloying different semiconductors to continuously tune the band gap and band-edge energies. Implementation of this approach in organic semiconductors has been hindered by strong localization of the electronic states in these materials. We show that the influence of so far largely ignored long-range Coulomb interactions provides a workaround. Photoelectron spectroscopy confirms that the ionization energies of crystalline organic semiconductors can be continuously tuned over a wide range by blending them with their halogenated derivatives. Correspondingly, the photovoltaic gap and open-circuit voltage of organic solar cells can be continuously tuned by the blending ratio of these donors.

Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction.

Abstract: Microfluidic organ-on-a-chip technology aims to replace animal toxicity testing, but thus far has demonstrated few advantages over traditional methods. Mitochondrial dysfunction plays a critical role in the development of chemical and pharmaceutical toxicity, as well as pluripotency and disease processes. However, current methods to evaluate mitochondrial activity still rely on end-point assays, resulting in limited kinetic and prognostic information. Here, we present a liver-on-chip device capable of maintaining human tissue for over a month in vitro under physiological conditions. Mitochondrial respiration was monitored in real time using two-frequency phase modulation of tissue-embedded phosphorescent microprobes. A computer-controlled microfluidic switchboard allowed contiguous electrochemical measurements of glucose and lactate, providing real-time analysis of minute shifts from oxidative phosphorylation to anaerobic glycolysis, an early indication of mitochondrial stress. We quantify the dynamics of cellular adaptation to mitochondrial damage and the resulting redistribution of ATP production during rotenone-induced mitochondrial dysfunction and troglitazone (Rezulin)-induced mitochondrial stress. We show troglitazone shifts metabolic fluxes at concentrations previously regarded as safe, suggesting a mechanism for its observed idiosyncratic effect. Our microfluidic platform reveals the dynamics and strategies of cellular adaptation to mitochondrial damage, a unique advantage of organ-on-chip technology.

Charge-Trapping Phenomena in HfO 2 -Based FeFET-Type Nonvolatile Memories

Abstract: Ferroelectric field effect transistors (FeFETs) based on ferroelectric hafnium oxide (HfO2) thin films show high potential for future embedded nonvolatile memory applications. However, HfO2 films besides their recently discovered ferroelectric behavior are also prone to undesired charge trapping effects. Therefore, the scope of this paper is to verify the possibility of the charge trapping during standard operation of the HfO2-based FeFET memories. The kinetics of the charge trapping and its interplay with the ferroelectric polarization switching are analyzed in detail using the single-pulse $I_{D}$ – $V_{G}$ technique. Furthermore, the impact of the charge trapping on the important memory characteristics such as retention and endurance is investigated.

Making sense of big data in health research: Towards an EU action plan

Abstract: Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of “big data” for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health and healthcare for all Europeans.

UUV Simulator: A Gazebo-based package for underwater intervention and multi-robot simulation

Abstract: This paper describes the Unmanned Underwater Vehicle (UUV) Simulator, an extension of the open-source robotics simulator Gazebo to underwater scenarios, that can simulate multiple underwater robots and intervention tasks using robotic manipulators. This is achieved mainly through a set of newly implemented plugins that model underwater hydrostatic and hydrodynamic effects, thrusters, sensors, and external disturbances. In contrast to existing solutions, it reuses and extends a general-purpose robotics simulation platform to underwater environments.

From theory to practice in smart specialization strategy: emerging limits and possible future trajectories

Abstract: The smart specialization strategy is now a reality. With regions and nations having completed the technical fulfillment of the ex-ante conditionality and the related action plans, the first evaluation studies have been launched with the aim to assess the consistency of the concept, once moving from the design (theory) to the implementation phase (practice). From these first evaluation exercises, strengths and weaknesses emerge in the way the smart specialization strategy has been conceived that lead to reflections on its possible future adjustment trends. The paper highlights emerging bottlenecks (e.g. the lack of local pre-conditions in the local economy and limits of governance) as well as possible future trajectories to overcome such bottlenecks, like the shift from a compulsory to a voluntary RIS, and from an industry-focused to a territorial development strategies.

Nonlinear aging of cylindrical lithium-ion cells linked to heterogeneous compression

Abstract: Second-life applications of automotive lithium-ion batteries are currently investigated for grid stabilization. Reutilization depends on reliable projections of the remaining useful life. However, reports on sudden degradation of lithium-ion-cells near 80% state of health challenge these extrapolations. Sudden degradation was demonstrated for different positive active materials. This work elucidates the cause of sudden degradation in detail. As part of a larger study on nonlinear degradation, in-depth analyses of cells with different residual capacities are performed. Sudden degradation of capacity is found to be triggered by the appearance of lithium plating confined to small characteristic areas, generated by heterogeneous compression. The resulting lithium loss rapidly alters the balancing of the electrodes, thus generating a self-amplifying circle of active material and lithium loss. Changes in impedance and open-circuit voltage are explained by the expansion of degraded patches. Destructive analysis reveals that sudden degradation is caused by the graphite electrode while the positive electrode is found unchanged except for delithiation caused by side reactions on the negative electrode. Our findings illustrate the importance of homogeneous compression of the electrode assembly and carbon electrode formulation. Finally, a quick test to evaluate the vulnerability of cell designs toward sudden degradation is proposed.

Considerations of Environmentally Relevant Test Conditions for Improved Evaluation of Ecological Hazards of Engineered Nanomaterials

Abstract: Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant concentrations-where observing outcomes is difficult-versus higher ENM doses, where responses are observable What exposure conditions are typically used in assessing ENM hazards to populations? What conditions are used to test ecosystem-scale hazards? What is known regarding actual ENMs in the environment, via measurements or modeling simulations? How should exposure conditions, ENM transformation, dose, and body burden be used in interpreting biological and computational findings for assessing risks? These questions were addressed in the context of this critical review As a result, three main recommendations emerged First, researchers should improve ecotoxicology of ENMs by choosing test end points, duration, and study conditions-including ENM test concentrations-that align with realistic exposure scenarios Second, testing should proceed via tiers with iterative feedback that informs experiments at other levels of biological organization Finally, environmental realism in ENM hazard assessments should involve greater coordination among ENM quantitative analysts, exposure modelers, and ecotoxicologists, across government, industry, and academia