Risks of Using Improper Priors with Gibbs Sampling and Autocorrelated Errors

Abstract

In this article we examine the use of Gibbs sampling to estimate the autocorrelation coefficient in a linear regression model. Researchers had previously experienced difficulty with moderate-to-high positive autocorrelated errors; estimates could be unstable and sometimes failed to converge. We show that the cause of this problem is that the use of an improper prior leads to an improper posterior, although the conditionals are proper, and hence a formal Gibbs sampler can be constructed. The problem is solved by the use of a vague but proper prior. In this simple case many of the calculations can be done analytically and it serves as a warning as to the uncritical use of improper priors with Gibbs sampling.     

Site-selective glycosylation of hemoglobin with variable molecular weight oligosaccharides: potential alternative to PEGylation

Poly(ethylene glycol) (PEG) conjugation (i.e., PEGylation) is a commonly used strategy to increase the circulatory half-life of therapeutic proteins and colloids; however, few viable alternatives exist to replicate its functions. Herein, we report a method for the rapid site-selective glycosylation of proteins with variously sized carbohydrates, up to a molecular weight (MW) of 10,000, thus serving as a potential alternative for PEGylation. More importantly, the method developed has two unique features. First, traditional protecting group strategies that typically accompany the modification of the carbohydrate fragments are circumvented, allowing for the facile site-selective glycosylation of a desired protein with variously sized glycans. Second, the methodology employed is not limited by oligosaccharide size; consequently, glycans of MW similar to that of PEG, used in the PEGylation of therapeutic proteins, can be employed. To demonstrate the usefulness of this technology, hemoglobin (Hb) was site-selectively glycosylated with a series of carbohydrates of increasing MW (from 504 to ～10,000). Hb was selected on the basis of the vast wealth of biochemical and biophysical knowledge present in the literature and because of its use as a precursor in the synthesis/formulation of artificial red blood cell substitutes. Following the successful site-selective glycosylation of Hb, the impact of increasing the glycan MW on Hb's biophysical properties was investigated in vitro.     

High resolution mass spectrometry. Bufadienolides—II.

Complete low resolution mass spectra and high resolution data for selected important peaks are presented and discussed for a series of naturally occurring 14β, 15β-epoxybufadienolides (toad poisons) and their derivatives. The compounds examined were resibufogenin, marinobufagin, cinobufagin, desacetylcinobufagin, cinobufotalin, desacetylcinobufotalin and resibufagin, and the derivatives were 11α-hydroxyresibufogenin, 3β-acetoxymarinobufagin, 3-ketocinobufagin, 3β-acetoxy-16β-desacetylcinobufagin, 3β-acetoxy-16-ketocinobufagin, resibufaginol, 14α-artebufogenin and 3β-suberyloxyresibufogenin methyl ester. The relatively unsaturated 2-pyrone group of C-17β has been used as an integral label to distinguish (from elemental composition data) ions containing it from those arising in other parts of the molecule that do not, and the spectra are interpreted in terms of structural ‘ion types’.     

Vibrational spectra and ab initio molecular orbital calculations of the novel anti-cancer drug combretastatin A-4 prodrug

The NIR-FT Raman and FT-IR spectral studies of the novel antineoplastic and antiangiogenesis substance comprestatin A-4 prodrug (CA4P) were carried out. The equilibrium geometry, various bonding features and harmonic vibrational frequencies of CA4P have been investigated with the help of B3LYP density functional theory (DFT) method. The most preferred cis-configuration for its bioactivity has been demonstrated on the basis of torsional potential energy surface (PES) scan studies. Stability of the molecule arising from hyperconjugative interactions leading to its bioactivity, charge delocalization and mesomeric effects have been analyzed using natural bond orbital (NBO) analysis. Detailed assignments of the vibrational spectra have been made with the aid of theoretically predicted vibrational frequencies. The optimized geometry shows near-planarity of phenyl rings and perpendicular conformation of meta substituted methoxy group. The vibrational analysis confirms the differently acting ring modes, steric repulsion, pi conjugation and back-donation.     

(+)-Phorboxazole A synthetic studies. Identification of a series of highly cytotoxic C(45-46) analogues

[structure: see text] Effective, scalable total syntheses and biological evaluation of six phorboxazole A analogues (1-6) have been achieved. Importantly, the C(45-46)-saturated, C(45-46)-alkenyl, and the C(45-46)-E-chloroalkenyl congeners (4, 5, and 6, respectively) reveal low nanomolar tumor cell growth inhibitory activity (GI50's) similar to or, in some cell lines, greater than that of the phorboxazoles across a diverse panel of human cancer cell lines.