Effects of Hofmeister anions on the aggregation behavior of PEO-PPO-PEO triblock copolymers

The effects of a series of Hofmeister anions on the phase behaviors of a poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer were investigated with an automated melting point system. Well hydrated anions and poorly hydrated anions interacted with the polymer differently and further affected the phase transition of the polymer. Poorly hydrated anions worked through changing the interfacial tension at the polymer/aqueous interface and in enhancing the polymer hydration by ion binding. The phase transition of the polymer in the presence of well hydrated anions correlated directly to the hydration entropy of the anions. As a consequence, the polymer showed a two-step phase transition in solutions containing poorly hydrated anions while displayed a single-step phase transition in the presence of well hydrated anions. The mechanisms of how ions interact with the polymer and further modulate its phase behaviors were discussed.     

Robust data imputation

Single imputation methods have been wide-discussed topics among researchers in the field of bioinformatics. One major shortcoming of methods proposed until now is the lack of robustness considerations. Like all data, gene expression data can possess outlying values. The presence of these outliers could have negative effects on the imputated values for the missing values. Afterwards, the outcome of any statistical analysis on the completed data could lead to incorrect conclusions. Therefore it is important to consider the possibility of outliers in the data set, and to evaluate how imputation techniques will handle these values. In this paper, a simulation study is performed to test existing techniques for data imputation in case outlying values are present in the data. To overcome some shortcomings of the existing imputation techniques, a new robust imputation method that can deal with the presence of outliers in the data is introduced. In addition, the robust imputation procedure cleans the data for further statistical analysis. Moreover, this method can be easily extended towards a multiple imputation approach by which the uncertainty of the imputed values is emphasised. Finally, a classification example illustrates the lack of robustness of some existing imputation methods and shows the advantage of the multiple imputation approach of the new robust imputation technique.     

Incorporation of 2,3-Disubstituted-1,4-Naphthoquinones into the A1 Binding Site of Photosystem I Studied by EPR and ENDOR Spectroscopy

Transient electron paramagnetic resonance and pulsed electron-nuclear double resonance (ENDOR) spectra of the state $ P_{700}^{ \cdot + } A_{1}^{ \cdot - } $ in photosystem I containing a series of non-native naphthoquinones (NQs) are presented. Previous studies have shown that quinones bind to the A₁ site with only one of their carbonyl groups H-bonded to the protein and that the asymmetric H-bond produces an odd alternant distribution of the spin density within the quinone. It is known that the native phylloquinone binds with its methyl group meta and its phytyl tail ortho to the H-bonded carbonyl. Monosubstituted NQs with short alkyl chains have been found to bind preferentially with their alkyl side groups meta to the H-bonded carbonyl. The selectivity of the binding site toward methyl and short chain substituents is studied by incorporating disubstituted NQs that have a methyl group at the 2-position and a short chain at the 3-position of the quinone ring. The hyperfine couplings (hfcs) of the methyl group protons are sensitive to the spin density distribution on the quinone and are used to deduce the position of the methyl group relative to the H-bonded carbonyl. The measured methyl proton hfcs indicate that the disubstituted quinones bind exclusively with their methyl group in the meta position relative to the H-bonded carbonyl and no evidence for binding with the methyl group in the ortho position is found. The disubstituted quinones have also been chosen to study the effect of electron withdrawing substituents on the spin density distribution. When the short chain contains electronegative atoms such as sulfur or chlorine, the methyl proton hfcs of the quinone in the A₁ binding site are found to be significantly larger than those of 2-methyl-1,4-naphthoquinone and phylloquinone in the same environment. Solution ENDOR measurements of the quinone radical anions in isopropanol and density functional theory (DFT) calculations in vacuo show that this increase in the hfcs is mostly intrinsic to the quinones due to the electron-withdrawing ability of the short chain and is not a result of differences in the binding to the protein. The DFT calculations suggest that the main reason for the increased methyl proton hfcs is delocalization of the singly occupied molecular orbital onto the side chain, which leads to an increase of the spin density on the neighboring carbon, which carries methyl group.     

Theory-guided design of Brønsted acid-assisted phosphine catalysis: synthesis of dihydropyrones from aldehydes and allenoates

The phosphine-catalyzed addition of 2,3-butadienoates to aldehydes has been extended to the formation of disubstituted dihydro-2-pyrones. The requisite shift in equilibrium of the intermediate zwitterionic β-phosphonium dienolates toward the s-cis intermediate was accomplished through the use of a Brønsted acid additive, which disrupts the favorable Coulombic interaction present in the s-trans intermediate. The detailed nature of the synergistic interactions involving the Brønsted acid additives and phosphine involved in the formation of s-cis β-phosphonium dienolates was analyzed through a series of DFT calculations. Unlike previously reported annulations of aldehydes with allenoates, where trialkylphosphines are optimal catalysts, in this study triphenylphosphine was also found for the first time to be a suitable catalyst for the synthesis of dihydropyrones. This method provides a one-step route toward functionalized dihydropyrones from simple, stable starting materials. In addition, new reaction pathways of phosphine-catalyzed allene annulations are unveiled, with the formation of dihydropyrones being the first example of dual activation in this sphere.     

Sequential imputation for missing values

As missing values are often encountered in gene expression data, many imputation methods have been developed to substitute these unknown values with estimated values. Despite the presence of many imputation methods, these available techniques have some disadvantages. Some imputation techniques constrain the imputation of missing values to a limited set of genes, whereas other imputation methods optimise a more global criterion whereby the computation time of the method becomes infeasible. Others might be fast but inaccurate. Therefore in this paper a new, fast and accurate estimation procedure, called SEQimpute, is proposed. By introducing the idea of minimisation of a statistical distance rather than a Euclidean distance the method is intrinsically different from the thus far existing imputation methods. Moreover, this newly proposed method can be easily embedded in a multiple imputation technique which is better suited to highlight the uncertainties about the missing value estimates. A comparative study is performed to assess the estimation of the missing values by different imputation approaches. The proposed imputation method is shown to outperform some of the existing imputation methods in terms of accuracy and computation speed.     

Urea metal-organic frameworks as effective and size-selective hydrogen-bond catalysts

A new urea-containing metal-organic framework (MOF) was synthesized to act as a heterogeneous catalyst. Ureas are well-known for self-recognition and aggregation behavior, resulting in loss of catalytic competency. The catalyst spatial isolation achievable in a porous MOF environment suggests a potentially general solution. The combination of a symmetrical urea tetracarboxylate strut, 4,4'-bipyridine, and Zn(NO(3))(2)·6H(2)O under solvothermal conditions afforded a new microporous MOF (NU-601). This material is indeed an effective hydrogen-bond-donor catalyst for Friedel-Crafts reactions between pyrroles and nitroalkenes, whereas a homogeneous urea is much less competent. The higher rates of reaction of small substrates relative to larger ones with NU-601 strongly suggest that catalysis primarily occurs within the pores of this new material rather than on its exterior. To the best of our knowledge, this approach is the first example of specific engineering of successful hydrogen-bonding catalysis into a MOF material.     

Robustness properties of a robust partial least squares regression method

The presence of multicollinearity in regression data is no exception in real life examples. Instead of applying ordinary regression methods, biased regression techniques such as principal component regression and ridge regression have been developed to cope with such datasets. In this paper, we consider partial least squares (PLS) regression by means of the SIMPLS algorithm. Because the SIMPLS algorithm is based on the empirical variance-covariance matrix of the data and on least squares regression, outliers have a damaging effect on the estimates. To reduce this pernicious effect of outliers, we propose to replace the empirical variance-covariance matrix in SIMPLS by a robust covariance estimator. We derive the influence function of the resulting PLS weight vectors and the regression estimates, and conclude that they will be bounded if the robust covariance estimator has a bounded influence function. Also the breakdown value is inherited from the robust estimator. We illustrate the results using the MCD estimator and the reweighted MCD estimator (RMCD) for low-dimensional datasets. Also some empirical properties are provided for a high-dimensional dataset.     

Selective Targeting of Tumor and Stromal Cells By a Nanocarrier System Displaying Lipidated Cathepsin B Inhibitor

Cathepsin B (CtsB) is a lysosomal cysteine proteinase that is specifically translocated to the extracellular milieu during cancer progression. The development of a lipidated CtsB inhibitor incorporated into the envelope of a liposomal nanocarrier (LNC‐NS‐629) is described. Ex vivo and in vivo studies confirmed selective targeting and internalization of LNC‐NS‐629 by tumor and stromal cells, thus validating CtsB targeting as a highly promising approach to cancer diagnosis and treatment.