Substitution of the human beta-spectrin promoter for the human agamma-globin promoter prevents silencing of a linked human beta-globin gene in transgenic mice

During development, changes occur in both the sites of erythropoiesis and the globin genes expressed at each developmental stage. Previous work has shown that high-level expression of human beta-like globin genes in transgenic mice requires the presence of the locus control region (LCR). Models of hemoglobin switching propose that the LCR and/or stage-specific elements interact with globin gene sequences to activate specific genes in erythroid cells. To test these models, we generated transgenic mice which contain the human Agamma-globin gene linked to a 576-bp fragment containing the human beta-spectrin promoter. In these mice, the beta-spectrin Agamma-globin (betasp/Agamma) transgene was expressed at high levels in erythroid cells throughout development. Transgenic mice containing a 40-kb cosmid construct with the micro-LCR, betasp/Agamma-, psibeta-, delta-, and beta-globin genes showed no developmental switching and expressed both human gamma- and beta-globin mRNAs in erythroid cells throughout development. Mice containing control cosmids with the Agamma-globin gene promoter showed developmental switching and expressed Agamma-globin mRNA in yolk sac and fetal liver erythroid cells and beta-globin mRNA in fetal liver and adult erythroid cells. Our results suggest that replacement of the gamma-globin promoter with the beta-spectrin promoter allows the expression of the beta-globin gene. We conclude that the gamma-globin promoter is necessary and sufficient to suppress the expression of the beta-globin gene in yolk sac erythroid cells.     

Solidification of Silicon for Solar Cells

Silicon is the dominating material in solar cells. Monocrystalline and multicrystalline cells have approximately equal market shares and are produced from wafers, cut from single crystals produced by Czochralski (CZ) pulling or from polycrystalline ingots made by directional solidification, respectively. The present paper reviews how demands for lower cost, better yield, higher efficiency and use of less pure silicon in solar cells are addressed by advanced solidification processing. In monocrystalline solar silicon, careful growth control results in less point defects, and better efficiency. Continuous- or semi-continuous CZ growth processes are being developed for better productivity and lower cost. In multicrystalline solar silicon, extended defects such as dislocations and grain boundaries decrease efficiency, particularly in combination with new, less expensive, but more contaminated silicon feedstock. This problem is addressed by control of nucleation and growth of ingots with larger grains, preferred grain orientation and lower dislocation density.     

Detailed Insight into the Interaction of Bicyclic Somatostatin Analogue with Cu(II) Ions

Somatostatin analogues are useful pharmaceuticals in peptide receptor radionuclide therapy. In previous studies, we analyzed a new bicyclic somatostatin analogue (BCS) in connection with Cu(II) ions. Two characteristic sites were present in the peptide chain: the receptor- and the metal-binding site. We have already shown that this ligand can form very stable imidazole complexes with the metal ion. In this work, our aim was to characterize the intramolecular interaction that occurs in the peptide molecule. Therefore, we analyzed the coordination abilities of two cyclic ligands, i.e., P1 only with the metal binding site and P2 with both sites, but without the disulfide bond. Furthermore, we used magnetic circular dichroism (MCD) spectroscopy to better understand the coordination process. We applied this method to analyze spectra of P1, P2, and BCS, which we have described previously. Additionally, we analyzed the MCD spectra of P3 ligand, which has only the receptor binding site in its structure. We have unequivocally shown that the presence of the Phe-Trp-Lys-Thr motif and the disulfide bond significantly increases the metal binding efficiency.     

The Synthesis and Biological Evaluation of Multifunctionalised Derivatives of Noscapine as Cytotoxic Agents

Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, is a well‐known antitussive drug that has a relatively safe in vitro toxicity profile. Noscapine is also known to possess weak anticancer efficacy, and since its discovery, efforts have been made to design derivatives with improved potency. Herein, the synthesis of a series of noscapine analogues, which have been modified in the 6′, 9′, 1 and 7‐positions, is described. In a previous study, replacement of the naturally occurring N‐methyl group in the 6′‐position with an N‐ethylaminocarbonyl was shown to promote cell‐cycle arrest and cytotoxicity against three cancer cell lines. Here, this modification has been combined with other structural changes that have previously been shown to improve anticancer activity, namely halo substitution in the 9′‐position, regioselective O‐demethylation to reveal a free phenol in the 7‐position, and reduction of the lactone to the corresponding cyclic ether in the 1‐position. The incorporation of new aryl substituents in the 9′‐position was also investigated. The study identified interesting new compounds able to induce G2/M cell‐cycle arrest and that possess cytotoxic activity against the human prostate carcinoma cell line PC3, the human breast adenocarcinoma cell line MCF‐7, and the human pancreatic epithelioid carcinoma cell line PANC‐1. In particular, the ethyl urea cyclic ether noscapinoids and a compound containing a 6′‐ethylaminocarbonyl along with 9′‐chloro, 7‐hydroxy and lactone moieties exhibited the most promising biological activities, with EC₅₀ values in the low micromolar range against all three cancer cell lines, and these derivatives warrant further investigation.     

Control of grain size and -orientation in multi-crystalline silicon ingots

Two different cooling rates have been imposed during the early solidification of two multi-crystalline silicon ingots with 250mm diameter and 100mm height in a pilot scale directional solidification furnace. This has been done by opening a variable heat leak system below the crucible in order to achieve a high initial cooling rate in one of the ingots. The grain-structure and -orientation of these two ingots have been investigated by light microscopy (LM) and electron backscattered diffraction (EBSD), and their electrical properties by quasi-steady state photo-conductance (QSSPC) and surface photovoltage (SPV) method. The ingot with the high initial cooling rate shows predominantly grains which are significantly larger than what is usually found in mc-Si. The minority carrier diffusion lengths measured on the large grains in the ingot with high cooling rate show higher values than those measured on the ingot with smaller grains. These results indicate that principles of grain size and -orientation control in mc-Si ingots can be applied to a pilot scale furnace, and the potential for up-scaling to industrial ingots with improved electrical properties and, thus, higher solar cell conversion efficiency.     

New minimal-realisation algorithm from system Markov parameters

A method is given to determine a minimal realisation of a finite-dimensional linear time-invariant system from a finite set of Markov parameters (time moments). The novel feature of this approach is the direct determination of the roots of the minimal polynomial.     

Modeling of ultrasonic wave propagation in teeth using PSpice: a comparison with finite element models

Ultrasound is used extensively in the medical field for the detection and characterization of a variety of features in the human body. Finite element models used to understand ultrasonic wave propagation in teeth have been developed so that ultrasound techniques could be realized in dentistry. This paper presents a hypothesis that underlies one possible design of an ultrasonic tool that can be used in a clinical environment, as well as several models that describe acoustic field simulation, propagation, and interaction with the layers of several tooth structures. A complete PSpice model of a single-element transducer based on Redwood's version of Mason's equivalent circuit, a focusing lens, and a multi-layer tooth structure is used to illustrate the validity of this hypothesis. Transmission line theory is employed as a basis for the models of the piezoceramic, the lens, and the different tooth layers. Results clearly depict the transmission and reflection of the ultrasonic waves as they travel through the layers within the tooth structure and point out the noticeable similarity to longitudinal L-wave signatures produced by axisymmetric finite element models presented in earlier studies.     

Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver

Studies with tumor necrosis factor p55 receptor- and interleukin-6 (IL-6)-deficient mice have shown that IL-6 is required for hepatocyte proliferation and reconstitution of the liver mass after partial hepatectomy. The biological activities of IL-6 are potentiated when this cytokine binds soluble forms of its specific receptor subunit (sIL-6R) and the resulting complex interacts with the transmembrane signaling chain gp130. We show here that double transgenic mice expressing high levels of both human IL-6 and sIL-6R under the control of liver-specific promoters spontaneously develop nodules of hepatocellular hyperplasia around periportal spaces and present signs of sustained hepatocyte proliferation. The resulting picture is identical to that of human nodular regenerative hyperplasia, a condition frequently associated with immunological and myeloproliferative disorders. In high expressors, hyperplastic lesions progress with time into discrete liver adenomas. These data strongly suggest that the IL-6/sIL-6R complex is both a primary stimulus to hepatocyte proliferation and a pathogenic factor of hepatocellular transformation.