An optimization‐based undeflated PLS (OUPLS) method to handle missing data in the training set

Advances in sensory systems have led to many industrial applications with large amounts of highly correlated data, particularly in chemical and pharmaceutical processes. With these correlated data sets, it becomes important to consider advanced modeling approaches built to deal with correlated inputs in order to understand the underlying sources of variability and how this variability will affect the final quality of the product. Additional to the correlated nature of the data sets, it is also common to find missing elements and noise in these data matrices. Latent variable regression methods such as partial least squares or projection to latent structures (PLS) have gained much attention in industry for their ability to handle ill‐conditioned matrices with missing elements. This feature of the PLS method is accomplished through the nonlinear iterative PLS (NIPALS) algorithm, with a simple modification to consider the missing data. Moreover, in expectation maximization PLS (EM‐PLS), imputed values are provided for missing data elements as initial estimates, conventional PLS is then applied to update these elements, and the process iterates to convergence. This study is the extension of previous work for principal component analysis (PCA), where we introduced nonlinear programming (NLP) as a means to estimate the parameters of the PCA model. Here, we focus on the parameters of a PLS model. As an alternative to modified NIPALS and EM‐PLS, this paper presents an efficient NLP‐based technique to find model parameters for PLS, where the desired properties of the parameters can be explicitly posed as constraints in the optimization problem of the proposed algorithm. We also present a number of simulation studies, where we compare effectiveness of the proposed algorithm with competing algorithms. Copyright © 2014 John Wiley & Sons, Ltd.     

High-performance thin-layer chromatographic analysis for the simultaneous quantification of lupeol and ursolic acid in the methanolic fraction of four different species of Bauhinia

JPC – Journal of Planar Chromatography – Modern TLC - A high-performance thin-layer chromatography (HPTLC) method for the simultaneous quantitative determination of lupeol and ursolic...     

Leveraging an enzyme/artificial substrate system to enhance cellular persulfides and mitigate neuroinflammation

Persulfides and polysulfides, collectively known as the sulfane sulfur pool along with hydrogen sulfide (H₂S), play a central role in cellular physiology and disease. Exogenously enhancing these species in cells is an emerging therapeutic paradigm for mitigating oxidative stress and inflammation that are associated with several diseases. In this study, we present a unique approach of using the cell''s own enzyme machinery coupled with an array of artificial substrates to enhance the cellular sulfane sulfur pool. We report the synthesis and validation of artificial/unnatural substrates specific for 3-mercaptopyruvate sulfurtransferase (3-MST), an important enzyme that contributes to sulfur trafficking in cells. We demonstrate that these artificial substrates generate persulfides in vitro as well as mediate sulfur transfer to low molecular weight thiols and to cysteine-containing proteins. A nearly 100-fold difference in the rates of H₂S production for the various substrates is observed supporting the tunability of persulfide generation by the 3-MST enzyme/artificial substrate system. Next, we show that the substrate 1a permeates cells and is selectively turned over by 3-MST to generate 3-MST-persulfide, which protects against reactive oxygen species-induced lethality. Lastly, in a mouse model, 1a is found to significantly mitigate neuroinflammation in the brain tissue. Together, the approach that we have developed allows for the on-demand generation of persulfides in vitro and in vivo using a range of shelf-stable, artificial substrates of 3-MST, while opening up possibilities of harnessing these molecules for therapeutic applications.

A persulfide/hydrogen sulfide generation strategy through artificial substrates for 3-mercaptopyruvate sulfurtransferase (3-MST) is reported, which enhances cellular persulfides, attenuates reactive oxygen species (ROS), and alleviates inflammation.     

Cyclization/hydrosilylation of functionalized 1,6-diynes catalyzed by cationic platinum complexes containing bidentate nitrogen ligands

A 1:1 mixture of the platinum dimethyl diimine complex [PhN[double bond]C(Me)C(Me)[double bond]NPh]PtMe(2) (4a) and B(C(6)F(5))(3) catalyzed the cyclization/hydrosilylation of dimethyl dipropargylmalonate (1) and HSiEt(3) to form 1,1-dicarbomethoxy-3-methylene-4-(triethylsilylmethylene)cyclopentane (3) in 82% isolated yield with 26:1 Z:E selectivity. Platinum-catalyzed diyne cyclization/hydrosilylation tolerated a range of functional groups including esters, sulfones, acetals, silyl ethers, amides, and hindered ketones. Diynes that possessed propargylic substitution underwent facile cyclization/hydrosilylation to form silylated 1,2-dialkylidene cyclopentanes as mixtures of regioisomers. Diynes that possessed an electron-deficient internal alkyne underwent cyclization/hydrosilylation in moderate yield to form products resulting from silyl transfer to the less substituted alkyne. The silylated 1,2-dialkylidenecyclopentanes formed via diyne cyclization/hydrosilylation underwent a range of transformations including protodesilylation, Z/E isomerization, and [4 + 2] cycloaddition with dieneophiles.     

Nitric oxide prodrugs: diazeniumdiolate anions of hindered secondary amines

Nitric oxide prodrugs derived from hindered secondary amines were prepared. The decomposition patterns of these prodrugs indicate that alpha-methyl groups around the nitrogen bearing the diazeniumdiolate group prolong their half-life in aqueous buffer.     

Cell-permeable esters of diazeniumdiolate-based nitric oxide prodrugs

Although O(2)-(2,4-dinitrophenyl) derivatives of diazeniumdiolate-based nitric oxide (NO) prodrugs bearing a free carboxylic acid group were activated by glutathione to release NO, these compounds were poor sources of intracellular NO and showed diminished antiproliferative activity against human leukemia HL-60 cells. The carboxylic acid esters of these prodrugs, however, were found to be superior sources of intracellular NO and potent inhibitors of HL-60 cell proliferation.