Cybersecurity Architectural Analysis for Complex Cyber-Physical Systems

In the modern military’s highly interconnected and technology-reliant operational environment, cybersecurity is rapidly growing in importance. Moreover, as a number of highly publicized attacks have occurred against complex cyber-physical systems such as automobiles and airplanes, cybersecurity is no longer limited to traditional computer systems and IT networks. While architectural analysis approaches are critical to improving cybersecurity, these approaches are often poorly understood and applied in ad hoc fashion. This work addresses these gaps by answering the questions: 1. “What is cybersecurity architectural analysis?” and 2. “How can architectural analysis be used to more effectively support cybersecurity decision making for complex cyber-physical systems?” First, a readily understandable description of key architectural concepts and definitions is provided which culminates in a working definition of “cybersecurity architectural analysis,” since none is available in the literature. Next, we survey several architectural analysis approaches to provide the reader with an understanding of the various approaches being used across government and industry. Based on our proposed definition, the previously introduced key concepts, and our survey results, we establish desirable characteristics for evaluating cybersecurity architectural analysis approaches. Lastly, each of the surveyed approaches is assessed against the characteristics and areas of future work are identified

A first parameterization of the pore-structure dependent kinetic adsorption model for O2 adsorption in biomass conversion modeling

Mass transport properties of the oxidation and gasification agents O2, CO2, and H2O are highly relevant for the modeling of the conversion process of biomasses. Therefore, this study presents experimental investigations on the adsorption kinetics of O2 on a biomass char using a modified gravimetric sorption device. Based on this comprehensive set of adsorption kinetic data, a first parameterization of the pore-structure dependent kinetic adsorption (PSK) model for O2 adsorption is presented. This model intends to account for mass transport during biomass conversion in a more meaningful way as it is considered in conventional conversion models. With this parameterization, the model is capable of describing accurately the adsorption kinetics of O2 as a function of time, temperature, and pressure

Thermodynamic properties of sea air

Very accurate thermodynamic potential functions are available for fluid water, ice, seawater and humid air covering wide ranges of temperature and pressure conditions. They permit the consistent computation of all equilibrium properties as, for example, required for coupled atmosphere-ocean models or the analysis of observational or experimental data. With the exception of humid air, these potential functions are already formulated as international standards released by the International Association for the Properties of Water and Steam (IAPWS), and have been adopted in 2009 for oceanography by IOC/UNESCO. <br><br> In this paper, we derive a collection of formulas for important quantities expressed in terms of the thermodynamic potentials, valid for typical phase transitions and composite systems of humid air and water/ice/seawater. Particular attention is given to equilibria between seawater and humid air, referred to as "sea air" here. In a related initiative, these formulas will soon be implemented in a source-code library for easy practical use. The library is primarily aimed at oceanographic applications but will be relevant to air-sea interaction and meteorology as well. <br><br> The formulas provided are valid for any consistent set of suitable thermodynamic potential functions. Here we adopt potential functions from previous publications in which they are constructed from theoretical laws and empirical data; they are briefly summarized in the appendix. The formulas make use of the full accuracy of these thermodynamic potentials, without additional approximations or empirical coefficients. They are expressed in the temperature scale ITS-90 and the 2008 Reference-Composition Salinity Scale

Protein Expression, Characterization and Activity Comparisons of Wild Type and Mutant DUSP5 Proteins

Background The mitogen-activated protein kinases (MAPKs) pathway is critical for cellular signaling, and proteins such as phosphatases that regulate this pathway are important for normal tissue development. Based on our previous work on dual specificity phosphatase-5 (DUSP5), and its role in embryonic vascular development and disease, we hypothesized that mutations in DUSP5 will affect its function. Results In this study, we tested this hypothesis by generating full-length glutathione-S-transferase-tagged DUSP5 and serine 147 proline mutant (S147P) proteins from bacteria. Light scattering analysis, circular dichroism, enzymatic assays and molecular modeling approaches have been performed to extensively characterize the protein form and function. We demonstrate that both proteins are active and, interestingly, the S147P protein is hypoactive as compared to the DUSP5 WT protein in two distinct biochemical substrate assays. Furthermore, due to the novel positioning of the S147P mutation, we utilize computational modeling to reconstruct full-length DUSP5 and S147P to predict a possible mechanism for the reduced activity of S147P. Conclusion Taken together, this is the first evidence of the generation and characterization of an active, full-length, mutant DUSP5 protein which will facilitate future structure-function and drug development-based studies

Cobicistat as a Potential Booster of Ponatinib and Dasatinib Exposure in a CML Patient:A Case Study

The authors present a case of a 57-year-old patient with chronic myeloid leukemia who was treated with ponatinib and subsequently treated with dasatinib. The patient showed a major molecular response; however, the BCR-ABL1 signal increased with low ponatinib and dasatinib trough concentrations. Cobicistat was used as a pharmacokinetic booster to increase ponatinib and dasatinib exposure, as opposed to increasing the dose. However, ponatinib exposure was not sufficiently increased by cobicistat. The peak dasatinib concentration was successfully increased with cobicistat treatment. Dasatinib and cobicistat cotreatment induced a response in BCR-ABL1 PCR signal, was well tolerated, and led to a substantial reduction in drug costs.</p

Pyrrolidine in Drug Discovery: A Versatile Scaffold for Novel Biologically Active Compounds

The five-membered pyrrolidine ring is one of the nitrogen heterocycles used widely by medicinal chemists to obtain compounds for the treatment of human diseases. The great interest in this saturated scaffold is enhanced by (1) the possibility to efficiently explore the pharmacophore space due to sp3-hybridization, (2) the contribution to the stereochemistry of the molecule, (3) and the increased three-dimensional (3D) coverage due to the non-planarity of the ring\u2014a phenomenon called \u201cpseudorotation\u201d. In this review, we report bioactive molecules with target selectivity characterized by the pyrrolidine ring and its derivatives, including pyrrolizines, pyrrolidine-2-one, pyrrolidine-2,5-diones and prolinol described in the literature from 2015 to date. After a comparison of the physicochemical parameters of pyrrolidine with the parent aromatic pyrrole and cyclopentane, we investigate the influence of steric factors on biological activity, also describing the structure\u2013activity relationship (SAR) of the studied compounds. To aid the reader\u2019s approach to reading the manuscript, we have planned the review on the basis of the synthetic strategies used: (1) ring construction from different cyclic or acyclic precursors, reporting the synthesis and the reaction conditions, or (2) functionalization of preformed pyrrolidine rings, e.g., proline derivatives. Since one of the most significant features of the pyrrolidine ring is the stereogenicity of carbons, we highlight how the different stereoisomers and the spatial orientation of substituents can lead to a different biological profile of drug candidates, due to the different binding mode to enantioselective proteins. We believe that this work can guide medicinal chemists to the best approach in the design of new pyrrolidine compounds with different biological profiles