A Bayes Sampling Allocation Scheme for Stratified Finite Populations With Hyperbinomial Prior Distributions

When sampling is carried out independently for the K strata of a finite stratified dichotomous population (defectives vs. standard items), and the number Z_i of defectives per stratum sample is observed, the corresponding probability function for X = (X_i , …, x_K ) is the product of hypergeometric functions which depend on the sample sizes n_i , the stratum sizes N_i , and the number of defectives M_i in the stratum (i = 1, …, K). It is assumed that prior information is available about the M_i 's which can be expressed, by suitable choice of the parameters a_i and b_i , as the product of independent hyperbinomial functions.

In each stratum the cost per observation is a known constant. Using squared error loss function, the prior Bayes risk is found for the linear function of interest,

and the optimum allocation of sample sizes is found, the one for which the prior Bayes risk is minimum when the total sampling budget is fixed.     

Chemistry, biology, and QSAR studies of substituted biaryl hydroxamates and mercaptoacetamides as HDAC inhibitors-nanomolar-potency inhibitors of pancreatic cancer cell growth

The histone deacetylases (HDACs) are able to regulate gene expression, and inhibitors of the HDACs (HDACIs) hold promise in the treatment of cancer as well as a variety of neurodegenerative diseases. To investigate the potential for isoform selectivity in the inhibition of HDACs, we prepared a small series of 2,4'-diaminobiphenyl ligands functionalized at the para-amino group with an appendage containing either a hydroxamate or a mercaptoacetamide group and coupled to an amino acid residue at the ortho-amino group. A smaller series of substituted phenylthiazoles was also explored. Some of these newly synthesized ligands show low-nanomolar potency in HDAC inhibition assays and display micromolar to low-nanomolar IC(50) values in tests against five pancreatic cancer cell lines. The isoform selectivity of these ligands for class I HDACs (HDAC1-3 and 8) and class IIb HDACs (HDAC6 and 10) together with QSAR studies of their correlation with lipophilicity are presented. Of particular interest is the selectivity of the mercaptoacetamides for HDAC6.     

Growth and exopolysaccharide yield of Lactobacillus delbrueckii ssp. bulgaricus DSM 20081 in batch and continuous bioreactor experiments at constant pH

Some Lactobacillus delbrueckii ssp. bulgaricus strains are able to synthesize exopolysaccharides (EPS) and are therefore highly important for the dairy industry as starter cultures. The aim of this study was to investigate the nutritional requirements for growth and EPS production of Lactobacillus delbrueckii ssp. bulgaricus DSM 20081. A medium was developed from a semi-defined medium (SDM) in which glucose was replaced by lactose and different combinations of supplements (nucleobases, vitamins, salts, sodium formate and orotic acid) were added. Constant pH batch fermentation with the modified medium resulted in an EPS yield of approximately 210 mg glucose equivalents per liter medium. This was a 10-fold increase over flask cultivation of this strain in SDM. Although not affecting cell growth, the mixture of salts enhanced the EPS synthesis. Whereas EPS production was approximately 12 mg/g dry biomass without salt supplementation, a significantly higher yield (approximately 20 mg/g dry biomass) was observed after adding the salt mixture. In continuous fermentation, a maximal EPS concentration was obtained at a dilution rate of 0.31/h (80 mg EPS/L), which corresponded to a specific EPS production of 49 mg/g dry biomass.     

Polyethylenimine-carbon nanotube nanohybrids for siRNA-mediated gene silencing at cellular level

Carbon nanotubes (CNTs) covalently modified with low molecular weight polyethylenimine (PEI) are able to bind and deliver siRNA to cells with higher efficacy than a reference lipidic carrier. The performances of the nanohybrid are rationalized by the combination of the cell penetration and endosomal escape properties of CNTs and PEI, respectively.     

Functionalization of electrospun fibers of poly(ε-caprolactone) with star shaped NCO-poly(ethylene glycol)-<Emphasis Type="Italic">stat</Emphasis>-poly(propylene glycol) for neuronal cell guidance

Microfibers produced with electrospinning have recently been used in tissue engineering. In the development of artificial implants for nerve regeneration they are of particular interest as guidance structures for cell migration and axonal growth. Using electrospinning we produced parallel-orientated biocompatible fibers in the submicron range consisting of poly(ε-caprolactone) (PCL) and star shaped NCO-poly(ethylene glycol)-stat-poly(propylene glycol) (sPEG). Addition of the bioactive peptide sequence glycine-arginine-glycine-aspartate-serine (GRGDS) or the extracellular matrix protein fibronectin to the electrospinning solution resulted in functionalized fibers. Surface characteristics and biological properties of functionalized and non-functionalised fibers were investigated. Polymer solutions and electrospinning process parameters were varied to obtain high quality orientated fibers. A polymer mixture containing high molecular weight PCL, PCL-diol, and sPEG permitted a chemical reaction between hydroxyl groups of the diol and isocyanante groups of the sPEG. Surface analysis demonstrated that sPEG at the fiber surface minimized protein adhesion. In vitro experiments using dorsal root ganglia explants showed that the cell repellent property of pure PCL/sPEG fibers was overcome by functionalization either with GRGDS peptide or fibronectin. In this way cell migration and axonal outgrowth along fibers were significantly increased. Thus, functionalized electrospun PCL/sPEG fibers, while preventing non-specific protein adsorption, are a suitable substrate for biological and medical applications.