71 research outputs found
Cybersecurity Policy Rubric and Analysis for the State of Maine Electrical Transmission Grid
The State of Maine’s (SOM) electrical grid is aging. While there are public and private efforts to bring it up to date, gaps in cybersecurity policies and laws exist (NERC, n.d.; see also MPUC, n.d.; CISA, n.d.). This policy and law research may also apply to other states and the protection of their critical infrastructure. The researcher examined the grid’s controls, policies, and laws to determine the influence each exerts over the grid and where that influence presents vulnerabilities in security. The research focused on the controls, policies, and laws that play a role in protecting the grid. The researcher created and analyzed each procedure, approach, and regulation against a NIST five-function framework merged with the MITRE Adversarial Tactics, Aspects, and Common Knowledge (ATT&CK) model to observe and analyze what gaps or policies lack effectiveness or present risk (MITRE ATT&CK®. n.d.). The researcher utilized publicly available data and information from participating government agencies to discover and analyze current public policy regarding the cybersecurity of the State of Maine (SOM) Electrical Transmission Network. The study\u27s results present numerous policies designed around the NIST recommendations. These policies are robust and work against most adversarial strategies. These policies are compared against the Center of Information Security’s (CIS) Critical Control list to find any controls that the current policies and procedures have not covered. The researcher used the merged matrix to analyze each relevant policy from the SOM Office of Information Technology (OIT). The researcher designed the rubric to be improved and utilized to view policy from the perspective of the attacker in an efficient manner
N-body simulations of gravitational dynamics
We describe the astrophysical and numerical basis of N-body simulations, both
of collisional stellar systems (dense star clusters and galactic centres) and
collisionless stellar dynamics (galaxies and large-scale structure). We explain
and discuss the state-of-the-art algorithms used for these quite different
regimes, attempt to give a fair critique, and point out possible directions of
future improvement and development. We briefly touch upon the history of N-body
simulations and their most important results.Comment: invited review (28 pages), to appear in European Physics Journal Plu
A γ-lactam siderophore antibiotic effective against multidrug-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter spp.
Serious infections caused by multidrug-resistant (MDR) organisms (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii) present a critical need for innovative drug development. Herein, we describe the preclinical evaluation of YU253911, 2, a novel γ-lactam siderophore antibiotic with potent antimicrobial activity against MDR Gram-negative pathogens. Penicillin-binding protein (PBP) 3 was shown to be a target of 2 using a binding assay with purified P. aeruginosa PBP3. The specific binding interactions with P. aeruginosa were further characterized with a high-resolution (2.0 Å) X-ray structure of the compound's acylation product in P. aeruginosa PBP3. Compound 2 was shown to have a concentration >1 μg/ml at the 6 h time point when administered intravenously or subcutaneously in mice. Employing a meropenem resistant strain of P. aeruginosa, 2 was shown to have dose-dependent efficacy at 50 and 100 mg/kg q6h dosing in a mouse thigh infection model. Lastly, we showed that a novel γ-lactam and β-lactamase inhibitor (BLI) combination can effectively lower minimum inhibitory concentrations (MICs) against carbapenem resistant Acinetobacter spp. that demonstrated decreased susceptibility to 2 alone
A γ-Lactam Siderophore Antibiotic Effective against Multidrug-Resistant Gram-Negative Bacilli
Treatment of multidrug-resistant Gram-negative bacterial pathogens represents a critical clinical need. Here, we report a novel γ-lactam pyrazolidinone that targets penicillin-binding proteins (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of γ-lactam YU253434, 1, are reported along with the finding that 1 is resistant to hydrolysis by all four classes of β-lactamases. The druglike characteristics and mouse PK data are described along with the X-ray crystal structure of 1 binding to its target PBP3
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A conserved fungal glycosyltransferase facilitates pathogenesis of plants by enabling hyphal growth on solid surfaces
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Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants. However, the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form. During a random T-DNA mutagenesis screen performed on the pleomorphic wheat (Triticum aestivum) pathogen Zymoseptoria tritici, we acquired a mutant unable to extend hyphae specifically when on solid surfaces. In contrast “yeast-like” growth, and all other growth forms, were unaffected. The inability to extend surface hyphae resulted in a complete loss of virulence on plants. The affected gene encoded a predicted type 2 glycosyltransferase (ZtGT2). Analysis of >800 genomes from taxonomically diverse fungi highlighted a generally widespread, but discontinuous, distribution of ZtGT2 orthologues, and a complete absence of any similar proteins in non-filamentous ascomycete yeasts. Deletion mutants of the ZtGT2 orthologue in the taxonomically un-related fungus Fusarium graminearum were also severely impaired in hyphal growth and non-pathogenic on wheat ears. ZtGT2 expression increased during filamentous growth and electron microscopy on deletion mutants (ΔZtGT2) suggested the protein functions to maintain the outermost surface of the fungal cell wall. Despite this, adhesion to leaf surfaces was unaffected in ΔZtGT2 mutants and global RNAseq-based gene expression profiling highlighted that surface-sensing and protein secretion was also largely unaffected. However, ΔZtGT2 mutants constitutively overexpressed several transmembrane and secreted proteins, including an important LysM-domain chitin-binding virulence effector, Zt3LysM. ZtGT2 likely functions in the synthesis of a currently unknown, potentially minor but widespread, extracellular or outer cell wall polysaccharide which plays a key role in facilitating many interactions between plants and fungi by enabling hyphal growth on solid matrices
Dense Stellar Populations: Initial Conditions
This chapter is based on four lectures given at the Cambridge N-body school
"Cambody". The material covered includes the IMF, the 6D structure of dense
clusters, residual gas expulsion and the initial binary population. It is aimed
at those needing to initialise stellar populations for a variety of purposes
(N-body experiments, stellar population synthesis).Comment: 85 pages. To appear in The Cambridge N-body Lectures, Sverre Aarseth,
Christopher Tout, Rosemary Mardling (eds), Lecture Notes in Physics Series,
Springer Verla
The Physics of Star Cluster Formation and Evolution
© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00689-4.Star clusters form in dense, hierarchically collapsing gas clouds. Bulk kinetic energy is transformed to turbulence with stars forming from cores fed by filaments. In the most compact regions, stellar feedback is least effective in removing the gas and stars may form very efficiently. These are also the regions where, in high-mass clusters, ejecta from some kind of high-mass stars are effectively captured during the formation phase of some of the low mass stars and effectively channeled into the latter to form multiple populations. Star formation epochs in star clusters are generally set by gas flows that determine the abundance of gas in the cluster. We argue that there is likely only one star formation epoch after which clusters remain essentially clear of gas by cluster winds. Collisional dynamics is important in this phase leading to core collapse, expansion and eventual dispersion of every cluster. We review recent developments in the field with a focus on theoretical work.Peer reviewe
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