Evaluation of the degree of rate control via automatic differentiation

The degree of rate control (DRC) quantitatively identifies the kinetically relevant (sometimes known as rate-limiting) steps of a complex reaction network. This concept relies on derivatives which are commonly implemented numerically, for example, with finite differences (FDs). Numerical derivatives are tedious to implement, and can be problematic, and unstable or unreliable. In this study, we demonstrate the use of automatic differentiation (AD) in the evaluation of the DRC. AD libraries are increasingly available through modern machine learning frameworks. Compared with the FDs, AD provides solutions with higher accuracy with lower computational cost. We demonstrate applications in steady-state and transient kinetics. Furthermore, we illustrate a hybrid local-global sensitivity analysis method, the distributed evaluation of local sensitivity analysis, to assess the importance of kinetic parameters over an uncertain space. This method also benefits from AD to obtain high-quality results efficiently.     

A fast algorithm and practical considerations for passive macromodeling of measured/simulated data

Passive macromodeling of high-speed package and interconnect modules characterized by measured/simulated data has generated immense interest during the recent years. This paper presents an efficient algorithm for transient simulation of interconnect networks characterized by measured/simulated data in the presence of other linear and nonlinear devices. A new set of linear constraints are proposed, which help in preserving the passivity of resulting macromodels. Examples are presented to demonstrate the validity and efficiency of the proposed algorithm.     

Nitroarenes as Antitubercular Agents: Stereoelectronic Modulation to Mitigate Mutagenicity

Nitroarenes are less preferred in drug discovery due to their potential to be mutagenic. However, several nitroarenes were shown to be promising antitubercular agents with specific modes of action, namely, nitroimidazoles and benzothiazinones. The nitro group in these compounds is activated through different mechanisms, both enzymatic and non‐enzymatic, in mycobacteria prior to binding to the target of interest. From a whole‐cell screening program, we identified a novel lead nitrobenzothiazole (BT) series that acts by inhibition of decaprenylphosphoryl‐β‐d ‐ribose 2′‐epimerase (DprE1) of Mycobacterium tuberculosis (Mtb). The lead was found to be mutagenic to start with. Our efforts to mitigate mutagenicity resulted in the identification of 6‐methyl‐7‐nitro‐5‐(trifluoromethyl)‐1,3‐benzothiazoles (cBTs), a novel class of antitubercular agents that are non‐mutagenic and exhibit an improved safety profile. The methyl group ortho to the nitro group decreases the electron affinity of the series, and is hence responsible for the non‐mutagenic nature of these compounds. Additionally, the co‐crystal structure of cBT in complex with Mtb DprE1 established the mode of binding. This investigation led to a new non‐mutagenic antitubercular agent and demonstrates that the mutagenic nature of nitroarenes can be solved by modulation of stereoelectronic properties.     

Scattering Domain Passivity Verification and Enforcement of Delayed Rational Functions

This letter introduces new algorithms for passivity verification and compensation of macromodels constructed from delayed rational functions in the scattering domain. For passivity verification, a frequency-dependent generalized eigenvalue is formulated, which is used to accurately determine the regions of passivity violation. For passivity compensation, first order perturbation theory is used to iteratively perturb the residues of the system until passivity is achieved. Numerical results validating the proposed algorithms are presented.     

Fast Passivity Verification and Enforcement via Reciprocal Systems for Interconnects With Large Order Macromodels

With the ever increasing signal speeds, signal integrity issues of high-speed VLSI designs are presenting increasingly difficult challenges for state-of-the-art modeling and simulation tools. Consequently, characterization and passive macromodeling of high-speed modules such as interconnects, vias, and packages based on tabulated data are becoming important. This paper presents a fast algorithm for passivity verification and enforcement of large order macromodels of scattering parameter based multiport subnetworks. Numerous examples tested on this algorithm demonstrate a significant speed-up compared to the existing algorithms in the literature     

Compact Macromodeling of High-Speed Circuits via Delayed Rational Functions

This letter introduces a new method for compact macromodeling of high-speed circuits with long delays, characterized by tabulated time-domain data. The algorithm is based on partitioning the response and subsequently approximating each partition with a low-order sum-of-exponentials, delayed in time-domain. This results in a compact low-order macromodel in the form of delayed-differential equations, which can be efficiently analyzed using SPICE like simulators.     

Passive model reduction of multiport distributed interconnects

Signal integrity analysis has become imperative for high-speed designs. In this paper, we present a new technique to advance Krylov-space-based passive model-reduction algorithms to include distributed interconnects described by telegrapher's equations. Interconnects can be lossy, coupled, and can include frequency-dependent parameters. In the proposed scheme, transmission-line subnetworks are treated with closed-form stamps obtained using matrix-exponential Pade, where the coefficients describing the model are computed a priori and analytically. In addition, a technique is given to guarantee that the contribution of these stamps to the modified nodal analysis formulation leads to a passive macromodel     

Passivity verification in delay-based macromodels of electrical interconnects

This paper presents a new theory that addresses the issue of passivity in macromodels of electrical interconnects constructed based on the method of characteristics (MoC). The proposed approach develops a new algebraic test to check for passivity in macromodels generated using MoC. The theory behind the developed test is based on deriving the necessary and sufficient conditions for the loss of positive-realness in the admittance matrix of the developed macromodel. An algorithmic procedure is proposed to verify passivity of general macromodels derived from the MoC. The results presented in this paper can be employed to test for positive-realness in dynamical systems described by algebraic delay-differential equations with discrete commensurate delays.