Fabrication, assembly, and characterization of molecular electronic components

One of the ultimate miniaturizations in nanotechnology is molecular electronics, where devices will consist of individual molecules. There are many complications associated with the use of molecules in electronic devices, such as the electronic perturbations in the molecule associated with being bonded to an electrode, how electrons traverse the metal-molecule junction, and the difficulty of macroscopically addressing single to very few molecules. Whether fabricating a test structure or a usable device, the use of self-assembly is fundamental to the fabrication of molecular electronic devices. We will discuss how to fabricate self-assembled monolayers into test assemblies and how to use intermolecular interactions to direct molecules into desired positions to create nanostructures and to connect functional molecules to the outside world. These assemblies serve as test structures for measurements on single or bundled molecules. The development of several experimental techniques, including various scanning probes, mercury drop junctions, break junctions, nanopores, crossed wires, and other techniques using nanoparticles have enabled the ability to test these structures and make reproducible measurements on single molecules. Many of these methods have been developed to test molecules with potential for integration into devices such as oligo (phenylene-ethynylene) molecules and other /spl pi/-conjugated molecules, in ensemble or single-molecule measurements.     

Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene

The acid sphingomyelinase (ASM) gene, which has been implicated in ceramide-mediated cell signaling and atherogenesis, gives rise to both lysosomal SMase (L-SMase), which is reportedly cation-independent, and secretory SMase (S-SMase), which is fully or partially dependent on Zn2+ for enzymatic activity. Herein we present evidence for a model to explain how a single mRNA gives rise to two forms of SMase with different cellular trafficking and apparent differences in Zn2+ dependence. First, we show that both S-SMase and L-SMase, which contain several highly conserved zinc-binding motifs, are directly activated by zinc. In addition, SMase assayed from a lysosome-rich fraction of Chinese hamster ovary cells was found to be partially zinc-dependent, suggesting that intact lysosomes from these cells contain subsaturating levels of Zn2+. Analysis of Asn-linked oligosaccharides and of N-terminal amino acid sequence indicated that S-SMase arises by trafficking through the Golgi secretory pathway, not by cellular release of L-SMase during trafficking to lysosomes or after delivery to lysosomes. Most importantly, when Zn2+-dependent S-SMase was incubated with SMase-negative cells, the enzyme was internalized, trafficked to lysosomes, and became zinc-independent. We conclude that L-SMase is exposed to cellular Zn2+ during trafficking to lysosomes, in lysosomes, and/or during cell homogenization. In contrast, the pathway targeting S-SMase to secretion appears to be relatively sequestered from cellular pools of Zn2+; thus S-SMase requires exogeneous Zn2+ for full activity. This model provides important information for understanding the enzymology and regulation of L- and S-SMase and for exploring possible roles of ASM gene products in cell signaling and atherogenesis.     

Embryonic stem cells and hematopoietic stem cell biology

Two advances in murine embryonic stem (ES) cell technology and their applications for the study of hematopoietic stem cells (HSCs) are discussed in this article. First, ES cells induced to differentiate in vitro form hematopoietic lineages in a fashion that recapitulates the ontogeny of blood formation in the embryo. This system offers a unique opportunity to isolate, examine, and manipulate the most primitive hematopoietic progenitors. Second, targeted gene ablation (knockout) studies in ES cells have identified several genes that are required for normal hematopoiesis and may function in the formation, maintenance, and differentiation of HSCs. Insights into murine hematopoiesis gained through the study of ES cells generally should be applicable to other vertebrates, including humans.     

HRTEM observation of the monoclinic-to-tetragonal m-t) phase transition in nanocrystalline ZrO2

The orientation relations m(100) || t(001), m[001] || t[110]; m(011) || t(100), m[100] || t[001]; m(100) || t(110), m[001] || t[001]; m(013) || t(116), m[001] || t[001] (indices for the primitive tetragonal cell) have been found between the tetragonal (t) and monoclinic (m) domains during the electron irradiation-induced m-t phase transition observed in-situ with HREM within isolated zirconia nanoparticles. Geometric models of the m-t interfaces are proposed.     

Representation of shift-invariant operators onL 2 byH ∞ transfer functions: An elementary proof,a generalization toL p,and a counterexample forL ∞

We give an elementary proof of the well-known fact that shift-invariant operators onL ²[0, ∞) are represented by transfer functions which are bounded and analytic on the right open half-plane. We prove a generalization to Banach space-valuedL ^p -functions, where 1≤p<∞. We show that the result no longer holds forp=∞. This research was supported partially by the Weizmann Fellowship, and partially by the Air Force Office of Scientific Research under Contract F49620-86-C-0111.     

Low Temperature Acoustic Properties of Poly-Crystalline Aluminium

As in other structurally disordered solids, the low temperature acoustic properties of poly-crystalline aluminium are governed by atomic two-level tunneling systems. The particular temperature variation of sound velocity and internal friction depends on the dynamical behaviour of these tunneling systems, which is expected to be determined by interaction with thermal phonons and conduction electrons as in metallic glasses. In earlier measurements on aluminium-wires no significant difference was found whether the sample was superconducting or kept in the normal state by a sufficiently high magnetic field and the concluding claim was ‘absence of electron-assisted relaxation for tunneling systems in poly-crystalline metals’. In this report, vibrating reed measurements are presented of pure poly-crystalline Al with a special sample shape that reduces the influence of the clamping. We in fact find significant differences between the sample being normal conducting or superconducting. The overall behaviour indeed resembles very closely that of metallic glasses and clearly demonstrates that also in Al tunneling systems couple to conduction electrons as expected. As a quantitative result we may state that the density of states of tunneling systems in poly-crystalline Al is considerably smaller than in metallic glasses. PACS numbers: 61.43.-j, 62.65.+k, 63.50.+x     

Relationship between the genomic organization and the overlapping embryonic expression patterns of the zebrafish dlx genes

To understand the relationship between the expression and the genomic organization of the zebrafish dlx genes, we have determined the genomic structure of the dlx2 and dlx4 loci. This led to the identification of the zebrafish dlx1 and dlx6 genes, which are closely linked to dlx2 and dlx4, respectively. Therefore, the inverted convergent configuration of Dlx genes is conserved among vertebrates. Analysis of the expression patterns of dlx1 and dlx6 showed striking similarities to those of dlx2 and dlx4, respectively, the genes to which they are linked. Furthermore, the expression patterns of dlx3 and dlx7, which likely constitute a third pair of convergently transcribed genes, are indistinguishable. Thus, the overlapping expression patterns of linked Dlx genes during embryonic development suggest that they share cis-acting sequences that control their spatiotemporal expression. The evolutionary conservation of the genomic organization and combinatorial expression of Dlx genes in distantly related vertebrates suggest tight control mechanisms that are essential for their function during development.