Detection of prion protein using a capillary electrophoresis-based competitive immunoassay with laser-induced fluorescence detection and cyclodextrin-aided separation

The development of capillary electrophoresis (CE)-based competitive immunoassay for prion protein (PrP) using carboxymethyl beta-cyclodextrin (CM-beta-CD) as a buffer additive is described here. The assay was based on the competitive binding of PrP and a fluorescein-labeled peptide from the prion protein with a limiting amount of specific antibody. The amount of both free and fluorescein-labeled peptide bound to antibody (immunocomplex) were determined by CE with laser-induced fluorescence detection. In the presence of PrP, the peak height ratio of the immunocomplex and the free peptide was altered compared to the control. These changes were directly proportional to the amount of PrP present. The fluorescently labeled peptide spanning amino acid positions 140-158 of the PrP and its corresponding monoclonal antibody is reported here. The reaction times of the antibody with either the peptide or the recombinant PrP was less than 1 min and is a large improvement over the 16-18 h required to achieve equilibrium for polyclonal antibodies. CM-beta-CD was explored as a buffer additive to suppress analyte adsorption and enhance separation selectivity in the CE analysis. A fast (1.1 min), selective (resolution 4.7), and reproducible (relative standard deviations of migration time for free and bound fluorescein isothiocyanate (FITC)-peptide 0.56% and 0.64%, respectively) separation was obtained with 0.6% CM-beta-CD in 25 mM N-tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid (TAPS) at pH 8.8. The concentration detection limit of the assay for recombinant PrP was determined to be 80 ng/mL (or mass detection limit 1 pg). When blood samples from scrapie-infected sheep and from normal sheep were tested, the results of the blood assay were consistent with scrapie status of the sheep as determined post mortem by Western blot analysis. Development of this assay will lead to a potentially robust, rapid, and specific preclinical diagnosis for transmissible spongiform encephalopathies (TSEs) in animals and humans.     

6种燕窝的傅里叶变换红外光谱法原性状快速鉴别

首次利用微钻石ATR探头傅里叶变换红外光谱法（FTIR）无损快速鉴别了6种燕窝。结果表明：印尼燕、越南燕、马来西亚燕、泰国血燕、菲律宾草燕和香港市售燕窝均有自己的红外特征谱,据谱图吸收峰的波数位置和相对峰强度的差异可达到燕窝类同和伪品和鉴别。该方法快速、简便、可靠。     

A structurally simple self-immolative reagent that provides three distinct, simultaneous responses per detection event

A general design is presented for a stimulus-responsive small molecule that is capable of responding to a specific applied chemical or physical signal by releasing two different types of pendant small molecules and a colorimetric indicator simultaneously. A key aspect of this design is the ease with which these reagents are prepared: typically, only four synthetic steps are required. Moreover, the modular construction strategy provides access to stimuli-responsive reagents that are capable of (i) responding to a variety of applied signals and (ii) releasing a number of different small molecules that contain primary alcohols, secondary alcohols, or phenols. These stimuli-responsive reagents are stable under physiological conditions (neither hydrolysis nor thermal degradation of the reagent occurs in significant quantity), and when they are exposed to the appropriate applied signal, they release both pendant small molecules and the colorimetric indicator completely within hours. Finally, unlike other functional groups, such as carbonates, that are used to connect alcohol-bearing molecules to controlled-release reagents, the linkage described in this article increases in hydrolytic stability (rather than decreases) as the pK(a) of the pendant alcohol decreases.     

Dynamic games in management science with interest rate uncertainty

This paper incorporates interest rate uncertainty in differential games applied in management science. A solution mechanism for games with uncertain interest rates is developed, and a novel characterizing the solution is established. This is the first time differential games with uncertain interest rates are developed and solved. An application in commercial resource extraction is provided. In particular, the impact of interest rate variations on the value of the firm is presented in a dynamic game framework. Numerical illustrations and computer generated results are presented. The analysis is also extended to cases with stochastic dynamics.     

Primary ion fluence dependence in time-of-flight SIMS of self-assembled monolayer of alkyl thiol molecules on Au(1 1 1)—Discussion of static limit

The nondestructive nature of static secondary ion mass spectrometry (SIMS) in the context of studies of self-assembled monolayers (SAMs) of organic molecules has been examined by measuring the primary ion fluence dependence of secondary ion signals with two well-known SAMs, C₁₈H₃₇SH on Au(1 1 1) and C₁₈H₃₇PO₃H₂ on freshly cleaved mica. This SIMS analysis is challenging because the bonding nature is delicate and the areal molecular density is less than 10¹⁵ cm⁻². In SIMS, it is prevalently assumed that if the primary ion fluence is confined to not more than 1 × 10¹² cm⁻², all secondary ion signals should not change by more than 10% and the practically defined static condition is satisfied. Our results from time-of-flight SIMS with the common primary ions of Bi₃⁺, Bi⁺ and Ar⁺, indicate that this prevalent static assumption fails for both model SAMs. The SIMS results from the phosphyl case, which have been recently published, consistently display the evidence of bombardment-induced damage. In comparison, the thiol case presented here shows much more complex primary ion fluence dependence of SIMS signals. It is therefore concluded that practical static analysis should use primary ion fluence not more than 1 × 10¹¹ cm⁻² or should simply record and report the effects of primary ion fluence.     

The Batchelor Spectrum for Mixing of Passive Scalars in Isotropic Turbulence

We examine the support for the Batchelor spectrum from well-resolved simulations of high-Schmidt-number mixing in isotropic turbulence, and resolve a conundrum with respect to the numerical value of the prefactor, also known as the Batchelor constant. Our conclusion is that the most probable value of the most compressive principal strain rate is more relevant than its mean, at least asymptotically.     

Nanoscale observation of morphological transformation during ageing of silica and silica-alumina

Atomic force microscopy (AFM) was used for in-situ observation of nanoscale morphological transformations during the ageing step in sol-gel synthesis. Silica, alumina and silica-alumina samples with different Si/Al ratios were prepared from inorganic salt precursors and geled at low pH. Silica and silica-alumina samples formed branch-like gel network made of nanometer-sized clusters. During ageing at room temperature, the overall structure of the gel network remained unchanged but the clusters underwent phase transformation, coaslesence, coarsening, fragmentation, as well as dissolution resulting in the internal restructuring of the gel material. Morphological transformation associated with crystallization of pseudo-boehmite phase was observed for the alumina samples. These nanometer-scale processes are expected to play a key role in dictating the material properties of the final sol-gel product.