Bit Penetration Into Rock-A Finite Element Study

The sequence of rock failure mechanisms and quantitative information on stress, displacement and material failure in the process of bit penetration have been obtained through computer simulation. A finite element approach has been developed to simulate bit penetration from bit-rock interaction to chip formation. A mathematical rock failure model, based on available rock failure experiments, has been proposed to represent post-failure rock behavior and applied in the penetration simulations. The finite element code was developed for two-dimensional plane strain problems to consider non-linear material properties, geometric non-linearity, and fracture propagation. An anistropic element as well as variable stiffness and stress release methods have been used. An iteration method, using an incremental displacement approach, has been applied for continuous penetration with modification of material properties and displacements. The simulation results of the blunt point bit are in reasonable agreement with penetration experiments on Limestone. Wedge and cylinder bit profiles have also been presented to demonstrate their shape effects. © 1976

Combined Thermal Weakening and Mechanical Disintegration of Hard Rock

This investigation of the combined effects of thermal weakening and mechanical disintegration (thermomechanical fragmentation) was initiated with a view toward better understanding of the processes required for more rapidly and economically fragmenting or excavating hard rock. Boring machines for utility tunnels, transportation tunnels or mining operations may be able to utilize the advantages of processes such as thermomechanical fragmentation. Secondary fragmentation or rock crushing processes also can conceivably employ the data obtained from this study

Elara: A Phase 2 Trial Investigating The Efficacy And Safety Of Tisagenlecleucel In Adult Patients With Refractory/Relapsed Follicular Lymphoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149492/1/hon6_2632.pd

Neuropathology in Mice Expressing Mouse Alpha-Synuclein

α-Synuclein (αSN) in human is tightly linked both neuropathologically and genetically to Parkinson's disease (PD) and related disorders. Disease-causing properties in vivo of the wildtype mouse ortholog (mαSN), which carries a threonine at position 53 like the A53T human mutant version that is genetically linked to PD, were never reported. To this end we generated mouse lines that express mαSN in central neurons at levels reaching up to six-fold compared to endogenous mαSN. Unlike transgenic mice expressing human wildtype or mutant forms of αSN, these mαSN transgenic mice showed pronounced ubiquitin immunopathology in spinal cord and brainstem. Isoelectric separation of mαSN species revealed multiple isoforms including two Ser129-phosphorylated species in the most severely affected brain regions. Neuronal Ser129-phosphorylated αSN occured in granular and small fibrillar aggregates and pathological staining patterns in neurites occasionally revealed a striking ladder of small alternating segments staining either for Ser129-phosphorylated αSN or ubiquitin but not both. Axonal degeneration in long white matter tracts of the spinal cord, with breakdown of myelin sheaths and degeneration of neuromuscular junctions with loss of integrity of the presynaptic neurofilament network in mαSN transgenic mice, was similar to what we have reported for mice expressing human αSN wildtype or mutant forms. In hippocampal neurons, the mαSN protein accumulated and was phosphorylated but these neurons showed no ubiquitin immunopathology. In contrast to the early-onset motor abnormalities and muscle weakness observed in mice expressing human αSN, mαSN transgenic mice displayed only end-stage phenotypic alterations that manifested alongside with neuropathology. Altogether these findings show that increased levels of wildtype mαSN does not induce early-onset behavior changes, but drives end-stage pathophysiological changes in murine neurons that are strikingly similar to those evoked by expression of human wildtype or mutant forms

Cyber-physical energy systems modeling, test specification, and co-simulation based testing

The gradual deployment of intelligent and coordinated devices in the electrical power system needs careful investigation of the interactions between the various domains involved. Especially due to the coupling between ICT and power systems a holistic approach for testing and validating is required. Taking existing (quasi-) standardised smart grid system and test specification methods as a starting point, we are developing a holistic testing and validation approach that allows a very flexible way of assessing the system level aspects by various types of experiments (including virtual, real, and mixed lab settings). This paper describes the formal holistic test case specification method and applies it to a particular co-simulation experimental setup. The various building blocks of such a simulation (i.e., FMI, mosaik, domain-specific simulation federates) are covered in more detail. The presented method addresses most modeling and specification challenges in cyber-physical energy systems and is extensible for future additions such as uncertainty quantification

An Integrated Research Infrastructure for Validating Cyber-Physical Energy Systems

Renewables are key enablers in the plight to reduce greenhouse gas emissions and cope with anthropogenic global warming. The intermittent nature and limited storage capabilities of renewables culminate in new challenges that power system operators have to deal with in order to regulate power quality and ensure security of supply. At the same time, the increased availability of advanced automation and communication technologies provides new opportunities for the derivation of intelligent solutions to tackle the challenges. Previous work has shown various new methods of operating highly interconnected power grids, and their corresponding components, in a more effective way. As a consequence of these developments, the traditional power system is being transformed into a cyber-physical energy system, a smart grid. Previous and ongoing research have tended to mainly focus on how specific aspects of smart grids can be validated, but until there exists no integrated approach for the analysis and evaluation of complex cyber-physical systems configurations. This paper introduces integrated research infrastructure that provides methods and tools for validating smart grid systems in a holistic, cyber-physical manner. The corresponding concepts are currently being developed further in the European project ERIGrid.Comment: 8th International Conference on Industrial Applications of Holonic and Multi-Agent Systems (HoloMAS 2017

Long-term research challenges in wind energy – a research agenda by the European Academy of Wind Energy

The European Academy of Wind Energy (eawe), representing universities and institutes with a significant wind energy programme in 14 countries, has discussed the long-term research challenges in wind energy. In contrast to research agendas addressing short- to medium-term research activities, this eawe document takes a longer-term perspective, addressing the scientific knowledge base that is required to develop wind energy beyond the applications of today and tomorrow. In other words, this long-term research agenda is driven by problems and curiosity, addressing basic research and fundamental knowledge in 11 research areas, ranging from physics and design to environmental and societal aspects. Because of the very nature of this initiative, this document does not intend to be permanent or complete. It shows the vision of the experts of the eawe, but other views may be possible. We sincerely hope that it will spur an even more intensive discussion worldwide within the wind energy community

Green and animal manure use in organic field crop systems

Dual-use cover/green manure (CGM) crops and animal manure are used to supply nitrogen (N) and phosphorus (P) to organically grown field crops. A comprehensive review of previous research was conducted to identify how CGM crops and animal manure have been used to meet N and P needs of organic field crops, and to identify knowledge gaps to direct future research efforts. Results indicate that: (a) CGM crops are used to provide N to subsequent cash crops in rotations; (b) CGM-supplied N generally can meet field crop needs in warm, humid regions but is insufficient for organic grain crops grown in cool and sub-humid regions; (c) adoption of conservation tillage practices can create or exacerbate N deficiencies; (d) excess N and P can result where animal manures are accessible if application rates are not carefully managed; and (e) integrating animal grazing into organic field crop systems has potential benefits but is generally not practiced. Work is needed to better understand the mechanisms governing the release of N by CGM crops to subsequent cash crops, and the legacy effects of animal manure applications in cool and sub-humid regions. The benefits and synergies that can occur by combining targeted animal grazing and CGMs on soil N, P, and other nutrients should be investigated. Improved communication and networking among researchers can aid efforts to solve soil fertility challenges faced by organic farmers when growing field crops in North America and elsewhere

Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: The OPTIPARK open-label study

BACKGROUND: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. METHODS: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). RESULTS: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. CONCLUSIONS: Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. TRIAL REGISTRATION: Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)