Resilient and agile engineering solutions to address societal challenges such as coronavirus pandemic

The world is witnessing tumultuous times as major economic powers including the US, UK, Russia, India, and most of Europe continue to be in a state of lockdown. The worst-hit sectors due to this lockdown are sales, production (manufacturing), transport (aerospace and automotive) and tourism. Lockdowns became necessary as a preventive measure to avoid the spread of the contagious and infectious “Coronavirus Disease 2019” (COVID-19). This newly identified disease is caused by a new strain of the virus being referred to as Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2; formerly called 2019-nCoV). We review the current medical and manufacturing response to COVID-19, including advances in instrumentation, sensing, use of lasers, fumigation chambers and development of novel tools such as lab-on-the-chip using combinatorial additive and subtractive manufacturing techniques and use of molecular modelling and molecular docking in drug and vaccine discovery. We also offer perspectives on future considerations on climate change, outsourced versus indigenous manufacturing, automation, and antimicrobial resistance. Overall, this paper attempts to identify key areas where manufacturing can be employed to address societal challenges such as COVID-19.     

Computation in gene networks

Genetic regulatory networks have the complex task of controlling all aspects of life. Using a model of gene expression by piecewise linear differential equations we show that this process can be considered as a process of computation. This is demonstrated by showing that this model can simulate memory bounded Turing machines. The simulation is robust with respect to perturbations of the system, an important property for both analog computers and biological systems. Robustness is achieved using a condition that ensures that the model equations, that are generally chaotic, follow a predictable dynamics.     

Gold(I)-catalyzed diastereo- and enantioselective 1,3-dipolar cycloaddition and Mannich reactions of azlactones

Azlactones participate in stereoselective reactions with electron-deficient alkenes and N-sulfonyl aldimines to give products of 1,3-dipolar cycloaddition and Mannich addition reactions, respectively. Both of these reactions proceed with good to excellent diastereo- and enantioselectivity using a single class of gold catalysts, namely C(2)-symmetric bis(phosphinegold(I) carboxylate) complexes. The development of the azlactone Mannich reaction to provide fully protected anti-α,β-diamino acid derivatives is described. 1,3-Dipolar cycloaddition reactions of several acyclic 1,2-disubstituted alkenes and the chemistry of the resultant cycloadducts are examined to probe the stereochemical course of this reaction. Reaction kinetics and tandem mass spectrometry studies of both the cycloaddition and Mannich reactions are reported. These studies support a mechanism in which the gold complexes catalyze addition reactions through nucleophile activation rather than the more typical activation of the electrophilic reaction component.     

Latent models for cross-covariance

We consider models for the covariance between two blocks of variables. Such models are often used in situations where latent variables are believed to present. In this paper we characterize exactly the set of distributions given by a class of models with one-dimensional latent variables. These models relate two blocks of observed variables, modeling only the cross-covariance matrix. We describe the relation of this model to the singular value decomposition of the cross-covariance matrix. We show that, although the model is underidentified, useful information may be extracted. We further consider an alternative parameterization in which one latent variable is associated with each block, and we extend the result to models with r-dimensional latent variables.     

Stereoselective aza-Diels-Alder reactions with 2H-azirines as dienophiles furnishing highly functionalized tetrahydropyridines

Highly diastereoselective Lewis acid mediated aza-Diels-Alder reactions of chiral auxiliary derivatized 2H-azirines have been accomplished for the first time, yielding bi and tri-cyclic heterocyclic compounds, comprising aziridine and tetrahydropyridine substructures, in up to 97% de; with the absolute stereochemistry of the major product confirmed by X-ray crystallography.     

Capillary electrophoretic and mass spectrometric analysis of a polydisperse fluorosurfactant

A fluorosurfactant has been studied using capillary electrophoresis and mass spectrometry. The fluorosurfactant, FC134, can be used as a buffer additive in capillary electrophoresis in order to decrease wall adsorption of proteins and in micellar electrokinetic chromatography. However, it has been discovered that this fluorosurfactant is polydisperse, thus containing substances with different lengths and structures. In this work, the fluorosurfactant sample components were separated by capillary electrophoresis. An uncoated as well as a poly(vinyl alcohol)-coated capillary were used with running electrolytes containing methanol and acetic acid. Following the capillary electrophoretic separation, fractions were collected for further analysis by MALDI-MS. Non-fractionated samples were also analyzed both by MALDI-MS and by ESI-MS.     

Capillary electrophoretic separation and fractionation of hydrophobic peptides onto a pre-structured matrix assisted laser desorption/ ionization target for mass spectrometric analysis

A CE separation of hydrophobic peptides followed by fractionation onto a prestructured MALDI target and off-line MS analysis was performed. An improved and partially automated manufacturing procedure of the previously described MALDI target is presented. This target is structurally coated with silicone and especially developed for hydrophobic peptides and proteins. Here, the target plate was designed specifically for the CE fraction collection. Different solvents were evaluated to meet the requirements of peptide solubility and compatibility to both the CE and MALDI methods and to the fractionation procedure. CE-MALDI-MS analysis of nine highly hydrophobic peptides from cyanogen bromide-digested bacteriorhodopsin is demonstrated.     

Investigation of Lewis acid-catalyzed asymmetric aza-Diels-Alder reactions of 2H-azirines

Asymmetric Diels-Alder reactions with 2H-azirines as dienophiles have been studied. Diastereoselective reactions with an enantiopure azirine 1b, bearing a chiral auxiliary, gave substituted bi- and tricyclic tetrahydropyridines in high yield and stereoselectivity, under the influence of a Lewis acid. The novel enantioselective [4+2] cycloaddition reaction of 3-benzyl-2H-azirine carboxylate with cyclopentadiene was investigated with various chiral Lewis acid complexes and provided the corresponding tetrahydropyridines in moderate to low yield and enantioselectivity.     

Modulation and the linewidth enhancement factor of a diode-pumped Nd:YVO4 laser

A technique based on an FM/AM method is proposed for measuring the linewidth enhancement factor a of a diode-pumped Nd:YVO4 laser. A standard rate equation model is complemented with temperature effects to explain the observed behavior under pump modulation. The result alpha = 0.25 +/- 0.13 agrees with values deduced from recent optical injection experiments.