Microsatellite instability analysis: a multicenter study for reliability and quality control

The molecular biology section of the Hereditary Non-Polyposis Colorectal Cancer study group-Germany, instituted a multicenter study to test the reliability and quality of microsatellite instability (MSI) analysis. Eight laboratories compared MSI analyses performed on 10 matched pairs of normal and tumor DNA from patients with colorectal carcinomas. A variety of techniques were applied to the detection of microsatellite changes: (a) silver and ethidium bromide staining of polyacrylamide gels; (b) radioactive labeling; and (c) automated fluorescence detection. The identification of highly unstable tumors and tumors without MSI was achieved in high concordance. However, the interpretation of the band patterns resulted in divergent classifications at several microsatellite marker loci for a large fraction of this tumor/normal panel. The data on more than 30 primers per case suggest that the enlargement of the microsatellite panel to more than 10 loci does not influence the results. In this study, cases with MSI in less than 10% of loci were classified as microsatellite stable, whereas MSI was diagnosed in cases with more than 40% of all markers unstable. We propose that a panel of five microsatellite loci consisting of repeats with different lengths should be analyzed in an initial analysis. When less than two marker loci display shifts in the microsatellite bands from tumor DNA, the panel should be enlarged to include an additional set of five marker loci. The number of marker loci analyzed as well as the number of unstable marker loci found should always be identified. These criteria should result in reports of MSI that are more comparable between studies.     

Crystallization and microstructural evolution of MgO–Al<Subscript>2</Subscript>O<Subscript>3</Subscript>–SiO<Subscript>2</Subscript>–TiO<Subscript>2</Subscript>–La<Subscript>2</Subscript>O<Subscript>3</Subscript> glass-ceramics

Crystallization and microstructure of glasses with the molar compositions 1MgO·1.2Al₂O₃·2.8SiO₂·1.2TiO₂·xLa₂O₃ (x = 0.1 and 0.4) were thermally treated at different temperatures in the range from 950 to 1250 °C and then analyzed by X-ray diffraction and scanning electron microscopy, in combination with energy-dispersive X-ray spectroscopy and electron backscatter diffraction. It was found that the microstructure is first homogeneous with the precipitation of randomly distributed crystals and then indialite domains with embedded perrierite and rutile crystals are formed. For higher temperatures or prolonged times, more domains appear and expand into the bulk of the sample. Finally, the entire sample consists of the indialite domains and the boundaries that are enriched in rutile, perrierite, and magnesium aluminotitanate. Nevertheless, very distinct differences are observed between the samples with different La₂O₃ concentrations. For the sample with x = 0.4, the domains were detected at lower temperatures, while the quantity and size of the domains increase faster due to the promoted precipitation of indialite. For the sample with x = 0.1, in addition to the domain boundaries, secondary boundaries between the “regions” (assemblages of the domains) are observed in a larger length scale. The average size of the crystalline phases found between the “regions” is larger than that typically observed at the domain boundaries. The sizes of the crystals at the boundaries decrease with higher concentrations of La₂O₃, and the crystals (especially perrierite) within the domains become larger, resulting in a more homogeneous microstructure. This results in better dielectric properties, i.e., much higher quality factor for the sample with x = 0.4 in comparison to that with x = 0.1 after heat-treatment at 1150 or 1250 °C.     

Biosynthetic studies on the macrolide antibiotic turimycin using 14C-labeled precursors

Using a strain of Streptomyces hygroscopicus JA 6599 several 14C-compounds were investigates as potential precursors of the macrolide antibiotic turimycin followed by partial degradation to localize the radioactivity. L-Methionine-14C-methyl and n-butyrate-1-14C were incorporated exclusively and in a specific manner. The incorporation ratios were dependent on the addition time of the precursors. Studies of the incorporation of acylmycaroses and demycarosyl turimycin into the antibiotic are also reported.     

Rapid unbiased bipolar incoherent calculator cube

Presented in this paper is one of several possible electrooptical engagement array architectures for performing matrix-matrix multiplication using incoherent light. Essential components of this new signal-processing device include two dynamic light valves operating in a reflection mode, a 2-D photodetector array, and a single polarizing beam splitter.     

A Fast and Simple Algorithm for the Money Changing Problem

The Money Changing Problem (MCP) can be stated as follows: Given k positive integers \(a_1< \cdots < a_k\) and a query integer M, is there a linear combination \(\sum_i c_ia_i = M\) with non-negative integers c_i, a decomposition of M? If so, produce one or all such decompositions. The largest integer without such a decomposition is called the Frobenius number g(a₁,...,a_k). A data structure called the residue table of a₁ words can be used to compute the Frobenius number in time O(a₁). We present an intriguingly simple algorithm for computing the residue table which runs in time O(ka₁), with no additional memory requirements, outperforming the best previously known algorithm. Simulations show that it performs well even on "hard" instances from the literature. In addition, we can employ the residue table to answer MCP decision instances in constant time, and a slight modification of size O(a₁) to compute one decomposition for a query M. Note that since both computing the Frobenius number and MCP (decision) are NP-hard, one cannot expect to find an algorithm that is polynomial in the size of the input, i.e., in k,log a_k, and log M. We then give an algorithm which, using a modification of the residue table, also constructible in O(ka₁) time, computes all decompositions of a query integer M. Its worst-case running time is O(ka₁) for each decomposition, thus the total runtime depends only on the output size and is independent of the size of query M itself. We apply our latter algorithm to interpreting mass spectrometry (MS) peaks: Due to its high speed and accuracy, MS is now the method of choice in protein identification. Interpreting individual peaks is one of the recurring subproblems in analyzing MS data; the task is to identify sample molecules whose mass the peak possibly represents. This can be stated as an MCP instance, with the masses of the individual amino acids as the k integers a₁,..., a_k. Our simulations show that our algorithm is fast on real data and is well suited for generating candidates for peak interpretation.     

Self-organized nano-crystallisation of BaF2 from Na2O/K2O/BaF2/Al2O3/SiO2 glasses

In glasses with the compositions (100 ? x)(2Na₂O·16K₂O·8Al₂O₃·74SiO₂)xBaF₂ (with x = 0 to 6), the glass transition temperature decreases with increasing BaF₂-concentration. Samples with x = 6 were thermally treated at temperatures in the range from 500 to 600 °C for 5–160 h. This leads to the crystallisation of BaF₂. The quantity of crystalline BaF₂ increases with increasing time of thermal treatment, while the mean crystallite size remains constant within the limits of error. The glass transformation temperature of partially crystallised samples increases with increasing crystallisation time and approaches a value equal to the temperature, at which the samples were treated. This is explained by the formation of a highly viscous layer enriched in SiO₂ which is formed during crystallisation. This layer acts as a diffusion barrier and hinders further crystal growth.     

The formation of strontium fluoride nano crystals from a phase separated silicate glass

The crystallization of nano crystalline rare earth or alkaline earth fluorides is of high importance for optically transparent partially crystalline materials. In this study, nano crystalline SrF₂ is precipitated. In contrast to recently studied glass systems which allow the crystallization of alkaline earth fluorides, droplet phase separation is the initial step of the SrF₂ crystallization. The large difference in the atomic number of strontium in comparison with the other glass components enables structural studies using electron microscopy. In a glass with the mol% composition 3.7Al₂O₃/12.3SrO/5.3K₂O/8.0Na₂O/60.3SiO₂/10.4SrF₂ nano crystalline SrF₂ is formed after annealing the glass samples at temperatures in the range from 520 to 600 °C for 2 to 160 h. The size of SrF₂ nano crystals remains constant within the limits of error and does neither depend on time nor on temperature. A highly viscous layer enriched in SiO₂ is formed during crystallization hindering further crystal growth.