A rapid and reliable method for Pb isotopic analysis of peat and lichens by laser ablation-quadrupole-inductively coupled plasma-mass spectrometry for biomonitoring and sample screening

An analytical protocol for rapid and reliable laser ablation-quadrupole (LA-Q)- and multi-collector (MC-) inductively coupled plasma-mass spectrometry (ICP-MS) analysis of Pb isotope ratios (²⁰⁷Pb/²⁰⁶Pb and ²⁰⁸Pb/²⁰⁶Pb) in peats and lichens is developed. This technique is applicable to source tracing atmospheric Pb deposition in biomonitoring studies and sample screening. Reference materials and environmental samples were dry ashed and pressed into pellets for introduction by laser ablation. No binder was used to reduce contamination. LA-MC-ICP-MS internal and external precisions were <1.1% and <0.3%, respectively, on both ²⁰⁷Pb/²⁰⁶Pb and ²⁰⁸Pb/²⁰⁶Pb ratios. LA-Q-ICP-MS internal precisions on ²⁰⁷Pb/²⁰⁶Pb and ²⁰⁸Pb/²⁰⁶Pb ratios were lower with values for the different sample sets <14.3% while external precisions were <2.9%. The level of external precision acquired in this study is high enough to distinguish between most modern Pb sources. LA-MC-ICP-MS measurements differed from thermal ionisation mass spectrometry (TIMS) values by 1% or less while the accuracy obtained using LA-Q-ICP-MS compared to solution MC-ICP-MS was 3.1% or better using a run bracketing (RB) mass bias correction method. Sample heterogeneity and detector switching when measuring ²⁰⁸Pb by Q-ICP-MS are identified as sources of reduced analytical performance.     

HNF4α Antagonists Discovered by a High-Throughput Screen for Modulators of the Human Insulin Promoter

Hepatocyte nuclear factor (HNF)4α is a central regulator of gene expression in cell types that play a critical role in metabolic homeostasis, including hepatocytes, enterocytes, and pancreatic β cells. Although fatty acids were found to occupy the HNF4α ligand-binding pocket and were proposed to act as ligands, there is controversy about both the nature of HNF4α ligands as well as the physiological role of the binding.?Here, we report the discovery of potent synthetic HNF4α antagonists through a high-throughput screen for effectors of the human insulin promoter. These molecules bound to HNF4α with high affinity and modulated the expression of known HNF4α target genes. Notably, they were found to be selectively cytotoxic to cancer cell lines in?vitro and in?vivo, although in?vivo potency was limited by suboptimal pharmacokinetic properties. The discovery of bioactive modulators for HNF4α raises the possibility that diseases involving HNF4α, such as diabetes and cancer, might be amenable to pharmacologic intervention by modulation of HNF4α activity.     

Temperature analysis of laser heated polymers on microsecond time scales

To investigate the temperature profiles on laser heated polymer films, we track the thermal radiation with 1 μs time and 1 μm spatial resolution. The resulting two-dimensional temperature graphs are compared to finite element simulations in order to understand the heat conversion and flow. The temperature measurement setup consists of a NIR laser and an optical detection system, which includes high performance optics and a microsecond gated camera, equipped with several interference filters. In this way the thermal radiation is detected in the visible range with spectral resolution. Fitting the spectrum with Planck’s law, two-dimensional micrographs of the temperature distribution are obtained. For polystyrene surfaces we were able to analyze the heating and the ablation behavior. Good agreement was found between experimental results and finite element simulations, when ablation is limited to a few tens of nanometers of the film thickness. Ablation of polystyrene starts at 150°C, 50 K above the glass transition temperature. We suggest a photomechanical ablation mechanism at that threshold fluence. For ablation at higher fluence and peak temperature, experiments indicate a thermal decomposition reaction. The temperature range of spinodal decomposition is not reached and can in our case be ruled out as ablation mechanism.     

First-principles optical spectra for F centers in MgO

The study of the oxygen vacancy (F center) in MgO has been aggravated by the fact that the positively charged and the neutral vacancy (F+ and F0, respectively) absorb at practically identical energies. Here we apply many-body perturbation theory in the G0W0 approximation and the Bethe-Salpeter approach to calculate the optical absorption and emission spectrum of the oxygen vacancy in all three charge states. We observe unprecedented agreement between the calculated and the experimental optical absorption spectra for the F0 and F+ center. Our calculations reveal that not only the absorption but also the emission spectra of different charge states peak at nearly the same energy, which leads to a reinterpretation of the F center's optical properties.     

Recording of IR spectra of polymer specimen surfaces with a rough relief using thermoplastic ATR elements

Possibilities of the ATR method are demonstrated which was suggested earlier to obtain IR spectra from specimens with a rough surface such as fibers, powders, nonwoven materials, and membranes. For this purpose a thermoplastic material chalcogenide glass IKS3) was used, which has a melting point of 70°C and was transparent from the near IR region to 12 μm. A prism manufactured of this material was heated to a softening temperature and then cooled to room temperature together with the pressed specimen, which ensured a quality contact between the ATR element and the object of study. The present results, first, demonstrated a possibility of obtaining a quality spectrum from a specimen with the depth of a surface roughtness that exceeds manyfolds the light wavelength and, second, revealed noticeable importance of the air gap between the optical element and the specimen, even in the case of a submicron surface relief. A. F. Ioffe Physico-Technical Institute, Russian Academy of Sciences, 26, Politekhnicheskaya St., St. Petersburg, 194021, Russia. Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 64, No. 1, pp. 132–136, January–February, 1997.     

Eine Klasse von 3-dimensionalen Mannigfaltigkeiten. II

Ohne ZusammenfassungDies ist der zweite Teil einer aus technischen Gründen aufgeteilten Arbeit. Kenntnis des ersten Teils ([13]) ist notwendig für die Lektüre des zweiten Teils. Hinweise der Art (,), mit<=5, beziehen sich auf den ersten Teil.     

Combinatorial Synthesis of Small Organic Molecules

Combinatorial synthesis has developed within a few years from a laboratory curiosity to a method that is taken seriously in drug research. Rapid progress in molecular biology and the resulting ability to determine the activity of new substances extremely efficiently have led to a change in paradigm for the synthesis of test compounds: in addition to the conventional procedure of synthesizing one substance after another, new methods allowing simultaneous creation of many structurally defined substances are becoming increasingly important. A characteristic of combinatorial synthesis is that a reaction is performed with many synthetic building blocks at once—in parallel or in a mixture— rather than with just one building block. All possible combinations are formed in each step, so that a large number of products, a so-called library, is obtained from only a few reactants. Several methods have been developed for combinatorial synthesis of small organic molecules, based on research into peptide library synthesis: single substances are produced by highly automated parallel syntheses, and special techniques enable targeted synthesis of mixtures with defined components. Many structures can be obtained by combinatorial synthesis, and the size of the libraries created ranges from a few individual compounds to many thousand substances in mixtures. This article gives an overview of the combinatorial syntheses of small organic molecules reported to date, performed both in solution and on a solid support. In addition, different techniques for identification of active compounds in mixtures are presented, together with ways to automate syntheses and process the large amounts of data produced. An overview of pionering companies active in this area is also given. The final outlook attempts to predict the future development of this exponentially growing area and the influence of this new thinking in other areas of chemistry.