muscleblind, a gene required for photoreceptor differentiation in Drosophila, encodes novel nuclear Cys3His-type zinc-finger-containing proteins

We have isolated the embryonic lethal gene muscleblind (mbl) as a suppressor of the sev-svp2 eye phenotype. Analysis of clones mutant for mbl during eye development shows that it is autonomously required for photoreceptor differentiation. Mutant cells are recruited into developing ommatidia and initiate neural differentiation, but they fail to properly differentiate as photoreceptors. Molecular analysis reveals that the mbl locus is large and complex, giving rise to multiple different proteins with common 5' sequences but different carboxy termini. Mbl proteins are nuclear and share a Cys3His zinc-finger motif which is also found in the TIS11/NUP475/TTP family of proteins and is highly conserved in vertebrates and invertebrates. Functional analysis of mbl, the observation that it also dominantly suppresses the sE-Jun(Asp) gain-of-function phenotype and the phenotypic similarity to mutants in the photoreceptor-specific glass gene suggest that mbl is a general factor required for photoreceptor differentiation.     

High-throughput, accurate mass metabolome profiling of cellular extracts by flow injection-time-of-flight mass spectrometry

Direct injection of samples on high-resolving mass spectrometers is an effective way to maximize analytical throughput and yet allow analyte discrimination in complex samples by mass-to-charge ratio. We present a platform of flow injection electrospray-time-of-flight mass spectrometry to profile small molecules in >1400 biological extracts per day at native mass resolution. We comprehensively benchmark the performance with more than 5000 injections of chemically defined standards and Escherichia coli cellular extracts obtained from miniscale cultivations. For at least 90% of tested compounds, we attain a linear response over 3 decades of concentration, interday coefficient of variation of <20%, and a mass accuracy of <0.001 amu. In polar Escherichia coli fractions, we reproducibly detected >1500 distinct ions in each mode. The accurate mass and correlation analysis enabled one to assign with good confidence 400-800 ions to electrospray derivatives of metabolites listed in the genome-wide reconstruction of Escherichia coli metabolism. Hence, we attain a coverage of about one-quarter of the total number of compounds listed in the reconstruction. Finally, we present an exemplary screen with Escherichia coli deletion mutants to show the exquisite capacity of the platform to identify lesions in primary metabolism at high throughputs.     

Conversion gain of m.e.s.f.e.t. drain mixers

A theoretical analysis of the gain properties of m.e.s.f.e.t. drain mixers is presented. The m.e.s.f.e.t. model includes the nonlinearity of both the transconductance and the drain resistance. For a special case, a simple analytical expression for the gain is given. Numerical results for a typical example are briefly presented as an illustration.     

Highly parallel mass fabrication and assembly of microdevices

 A process sequence for highly parallel manufacture and assembly of microdevices was developed and proven experimentally. By means of moulding or embossing a multitude of microstructures is built up on a common base plate in the first step. Subsequently, a plate-shape magazine with embedded microstructures is generated by a combination of casting and mechanical machining processes where the common base plate is removed. In this way, the microstructures become separated from each other by remain fixed and precisely positioned in the embedding material layer. Parallel assembly is now simply possible by pushing pins, which eject the microstructures from the magazine onto defined mounting positions of the microdevice to be assembled. The capacity of this process has been demonstrated by the manufacture of micro gear systems.     

Identification of some previously unknown aldehydes in cooked chicken

Aldehydes present in a flavor concentrate, obtained from cooked chicken were separated and isolated by means of gas liquid chromatography. Subsequently, they were converted into their 2,4-dinitrophenylhydrazones and identified by thin layer chromatography on Kieselguhr G-Carbowax 750 and Silica Gel G-AgNO₃ and by analysis after partial hydrogenation. Finally, they were compared with model substances. Besides the aldehydes which had been found earlier in cooked chicken the following new aldehydes were identified: 3-c-nonenal; 4-c-decenal; 2-t,4-c,7-c-decatrienal; 2-t,5-c-undecadienal; 2-t-dodecenal; 2-t,4-c-dodecadienal; 2-t,6-c- and 2-t,6-t-dodecadienal; 2-t-tridecenal; 2-t,4-c-tridecadienal; 2-t,4-c,7-c-tridecatrienal; and 2-t,4-c-tetradecadienal. Three of them, 4-c-decenal; 2-t,6-c-dodecadienal; and 2-t,4-c,7-c-tridecatrienal are typical breakdown products of arachidonic acid, and to a major extent also 2-t,5-c-undecadienal.     

Increased expression of cyclin D1 in a murine mammary epithelial cell line induces p27kip1, inhibits growth, and enhances apoptosis

Cyclin D1 is frequently amplified and/or overexpressed in human breast cancer and several other types of cancer. To examine the role of cyclin D1 in normal mammary epithelial cells, in the present study we have overexpressed human cyclin D1 in the mouse mammary epithelial cell line HC11, using retrovirus-mediated transduction. We found that the cyclin D1 overexpresser clones displayed a decrease in saturation density, a decrease in anchorage-independent growth, an increased fraction of cells in the G(zero)-G1 phase, and increased expression of beta-casein, when compared to the control cells. The latter finding suggested that they were more differentiated. Furthermore, the cyclin D1 overexpressers displayed a marked increase in susceptibility to induction of apoptosis by serum withdrawal or by treatment with hydroxyurea or the protein kinase C inhibitors CGP 41251 and Ro31-8220. Thus, in some mammary epithelial cells, increased expression of cyclin D1 can inhibit growth, induce differentiation, and enhance apoptosis. These effects might be due, at least in part, to the fact that these derivatives displayed increased expression of the p27kip1 inhibitory protein.     

Halogenated Bis(methoxybenzylidene)‐4‐piperidone Curcuminoids with Improved Anticancer Activity

A series of readily available curcuminoids with a halogenated bis(4‐methoxy/4,5‐dimethoxybenzylidene)‐4‐piperidone structure were prepared and analyzed for their cytotoxic impact on eight human cancer cell lines of five different entities. The known 3,4,5‐trimethoxybenzylidene curcuminoid 2 a and the new bis‐(3‐bromophenyl) and bis‐(3,5‐dibromophenyl) derivatives 3 c and 3 d proved to be more strongly antiproliferative than the known curcuminoid EF24 against six of these cell lines. Compounds 2 a and 3 c caused a distinct increase of reactive oxygen species, which eventually elicited apoptosis in 518A2 melanoma cells. Compound 2 a arrested 518A2 melanoma cells in G₁ phase of the cell cycle and had no effect on the expression of pro‐metastatic matrix metalloproteinases MMP‐2 and MMP‐9, whereas 3 c led to an accumulation of 518A2 cells in the G₂/M phase and to a downregulation of MMP‐2 expression. In addition, treatment with 2 a and 3 c resulted in significant inhibition of colony formation in HCT116 cells. Both 2 a and 3 c showed antiangiogenic activity, for example, by inhibiting the formation of sub‐intestinal veins (SIV) in zebrafish embryos. Compound 3 c was also well tolerated by mice and inhibited the growth of HCT116 colon cancer xenografts.     

A Systematic Approach for Ensuring the Logistic Process Reliability of Supply Chains

In the production logistics context, the process reliability of supply chains corresponds to their ability to meet the logistic performance expectations of customers. This ability depends on the contributions of all supply chain members to the logistic performance of the entire chain. The overall performance is affected by the dynamic Interrelationships between the specific logistic performances of the separate supply chain members. Currently, however, no practical analytical models of the logistic supply chain dynamics are available. This paper presents an approach for modeling and analysing the logistic interdependences across supply chains, the understanding of which enables supply chains to better control their process reliability.     

X-band balanced mixer using evanescent-mode circuitry

An X-Band balanced mixer using evanescent-mode circuitry has been developed utilising a waveguide magic-T. It shows an available conversion loss of 4.4 dB and a noise figure of 5.6 dB including a 1.2 dB noise contribution from an i.f. amplifier at a radio frequency of 8.61 GHz. Image and sum frequency are largely independently tunable.