Integrated Guidance and Control of Missiles with Θ-D Method

A new suboptimal control method is proposed in this study to effectively design an integrated guidance and control system for missiles. Optimal formulations allow designers to bring together concerns about guidance law performance and autopilot responses under one unified framework. They lead to a natural integration of these different functions. by modifying the appropriate cost functions, different responses, control saturations (autopilot related), miss distance (guidance related), etc., which are of primary concern to a missile system designer, can be easily studied. A new suboptimal control method, called the θ-D method, is employed to obtain an approximate closed-form solution to this nonlinear guidance problem based on approximations to the Hamilton-Jacobi-Bellman equation. Missile guidance law and autopilot design are formulated into a single unified state space framework. The cost function is chosen to reflect both guidance and control concerns. The ultimate control input is the missile fin deflections. A nonlinear six-degree-of-freedom (6-DOF) missile simulation is used to demonstrate the potential of this new integrated guidance and control approach

The influence of scavengers on VOC emissions in particleboards made from pine and poplar

This paper studies the performance of scavengers on Volatile Organic Compound (VOC) emissions from wood-based composites. Particleboards made from maritime pine (Pinus pinaster Ait.) and European poplar (Populus spp.) were produced with a UF resin doped with melamine and two scavengers, sodium metabisulfite and urea. VOC emission was measured according to EN ISO 16000. Particleboards made from pine present much higher total VOC (TVOC) emissions than boards made from poplar. Pine emits a higher amount of terpenes, but also aldehydes, acids and terpenoids, while poplar emits mainly acetic acid. Sodium metabisulfite showed an excellent ability to reduce aldehydes emission, which represents nearly 50 % of total emission of particleboards made from pine. When sodium metabisulfite was applied to particleboards made from poplar, reduction of TVOCs was not significant due to the low contribution of aldehydes to TVOCs. Urea presents a low reduction in TVOCs for both wood species

Gesamtdokumentation - Global Nachhaltige Kommune Schleswig-Holstein 2017-2020

GESAMTDOKUMENTATION - GLOBAL NACHHALTIGE KOMMUNE SCHLESWIG-HOLSTEIN 2017-2020 Gesamtdokumentation - Global Nachhaltige Kommune Schleswig-Holstein 2017-2020 / Butscher, Anke (Rights reserved) ( -

Finite-Horizon Robust Integrated Guidance-Control of A Moving-Mass Actuated Kinetic Warhead

A game-theoretic approach to the design of robust integrated guidance-control system for a moving-mass actuated kinetic warhead is presented. Feedback linearized form of the kinetic warhead dynamics and a high-order target model are used in the formulation. Nonlinear feedback solution to the robust finite-horizon target interception problem is derived using the recently developed multi-stepping algorithm. Due to its computational efficiency, the multi-stepping algorithm is suitable for real-time implementation. Interception of targets in the presence of modeling uncertainties is demonstrated in nonlinear engagement simulations

Development of actionable targets of multi-kinase inhibitors (AToMI) screening platform to dissect kinase targets of staurosporines in glioblastoma cells

Therapeutic resistance to kinase inhibitors constitutes a major unresolved clinical challenge in cancer and especially in glioblastoma. Multi-kinase inhibitors may be used for simultaneous targeting of multiple target kinases and thereby potentially overcome kinase inhibitor resistance. However, in most cases the identification of the target kinases mediating therapeutic effects of multi-kinase inhibitors has been challenging. To tackle this important problem, we developed an actionable targets of multi-kinase inhibitors (AToMI) strategy and used it for characterization of glioblastoma target kinases of staurosporine derivatives displaying synergy with protein phosphatase 2A (PP2A) reactivation. AToMI consists of interchangeable modules combining drug-kinase interaction assay, siRNA high-throughput screening, bioinformatics analysis, and validation screening with more selective target kinase inhibitors. As a result, AToMI analysis revealed AKT and mitochondrial pyruvate dehydrogenase kinase PDK1 and PDK4 as kinase targets of staurosporine derivatives UCN-01, CEP-701, and K252a that synergized with PP2A activation across heterogeneous glioblastoma cells. Based on these proof-of-principle results, we propose that the application and further development of AToMI for clinically applicable multi-kinase inhibitors could provide significant benefits in overcoming the challenge of lack of knowledge of the target specificity of multi-kinase inhibitors.Peer reviewe

Monotherapy efficacy of blood-brain barrier permeable small molecule reactivators of protein phosphatase 2A in glioblastoma

Glioblastoma is a fatal disease in which most targeted therapies have clinically failed. However, pharmacological reactivation of tumour suppressors has not been thoroughly studied as yet as a glioblastoma therapeutic strategy. Tumour suppressor protein phosphatase 2A is inhibited by non-genetic mechanisms in glioblastoma, and thus, it would be potentially amendable for therapeutic reactivation. Here, we demonstrate that small molecule activators of protein phosphatase 2A, NZ-8-061 and DBK-1154, effectively cross the in vitro model of blood-brain barrier, and in vivo partition to mouse brain tissue after oral dosing. In vitro, small molecule activators of protein phosphatase 2A exhibit robust cell-killing activity against five established glioblastoma cell lines, and nine patient-derived primary glioma cell lines. Collectively, these cell lines have heterogeneous genetic background, kinase inhibitor resistance profile and stemness properties; and they represent different clinical glioblastoma subtypes. Moreover, small molecule activators of protein phosphatase 2A were found to be superior to a range of kinase inhibitors in their capacity to kill patient-derived primary glioma cells. Oral dosing of either of the small molecule activators of protein phosphatase 2A significantly reduced growth of infiltrative intracranial glioblastoma tumours. DBK-1154, with both higher degree of brain/blood distribution, and more potent in vitro activity against all tested glioblastoma cell lines, also significantly increased survival of mice bearing orthotopic glioblastoma xenografts. In summary, this report presents a proof-of-principle data for blood-brain barrier-permeable tumour suppressor reactivation therapy for glioblastoma cells of heterogenous molecular background. These results also provide the first indications that protein phosphatase 2A reactivation might be able to challenge the current paradigm in glioblastoma therapies which has been strongly focused on targeting specific genetically altered cancer drivers with highly specific inhibitors. Based on demonstrated role for protein phosphatase 2A inhibition in glioblastoma cell drug resistance, small molecule activators of protein phosphatase 2A may prove to be beneficial in future glioblastoma combination therapies.Peer reviewe