The interface between silicon and a high-k oxide

The ability of the semiconductor industry to continue scaling microelectronic devices to ever smaller dimensions (a trend known as Moore's Law) is limited by quantum mechanical effects: as the thickness of conventional silicon dioxide (SiO(2)) gate insulators is reduced to just a few atomic layers, electrons can tunnel directly through the films. Continued device scaling will therefore probably require the replacement of the insulator with high-dielectric-constant (high-k) oxides, to increase its thickness, thus preventing tunnelling currents while retaining the electronic properties of an ultrathin SiO(2) film. Ultimately, such insulators will require an atomically defined interface with silicon without an interfacial SiO(2) layer for optimal performance. Following the first reports of epitaxial growth of AO and ABO(3) compounds on silicon, the formation of an atomically abrupt crystalline interface between strontium titanate and silicon was demonstrated. However, the atomic structure proposed for this interface is questionable because it requires silicon atoms that have coordinations rarely found elsewhere in nature. Here we describe first-principles calculations of the formation of the interface between silicon and strontium titanate and its atomic structure. Our study shows that atomic control of the interfacial structure by altering the chemical environment can dramatically improve the electronic properties of the interface to meet technological requirements. The interface structure and its chemistry may provide guidance for the selection process of other high-k gate oxides and for controlling their growth.     

Letters from William Burnside to Robert Fricke: automorphic functions,and the emergence of the Burnside Problem

Two letters from William Burnside have recently been found in the Nachlass of Robert Fricke that contain instances of the Burnside Problem prior to its first publication. We present these letters as a whole to the public for the first time. We draw a picture of these two mathematicians and describe their activities leading to their correspondence. We thus gain an insight into their respective motivations, reactions, and attitudes, which may sharpen the current understanding of professional and social interactions of the mathematical community at the turn of the twentieth century. Dedicated to Heiko Harborth on the occasion of his seventieth birthday.     

TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function

Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function.     

A photometric redshift of z = 6.39 +/- 0.12 for GRB 050904

Gamma-ray bursts (GRBs) and their afterglows are the most brilliant transient events in the Universe. Both the bursts themselves and their afterglows have been predicted to be visible out to redshifts of z approximately 20, and therefore to be powerful probes of the early Universe. The burst GRB 000131, at z = 4.50, was hitherto the most distant such event identified. Here we report the discovery of the bright near-infrared afterglow of GRB 050904 (ref. 4). From our measurements of the near-infrared afterglow, and our failure to detect the optical afterglow, we determine the photometric redshift of the burst to be z = 6.39 - 0.12 + 0.11 (refs 5-7). Subsequently, it was measured spectroscopically to be z = 6.29 +/- 0.01, in agreement with our photometric estimate. These results demonstrate that GRBs can be used to trace the star formation, metallicity, and reionization histories of the early Universe.     

Archimedean-like tiling on decagonal quasicrystalline surfaces

Monolayers on crystalline surfaces often form complex structures with physical and chemical properties that differ strongly from those of their bulk phases. Such hetero-epitactic overlayers are currently used in nanotechnology and understanding their growth mechanism is important for the development of new materials and devices. In comparison with crystals, quasicrystalline surfaces exhibit much larger structural and chemical complexity leading, for example, to unusual frictional, catalytical or optical properties. Deposition of thin films on such substrates can lead to structures that may have typical quasicrystalline properties. Recent experiments have indeed showed 5-fold symmetries in the diffraction pattern of metallic layers adsorbed on quasicrystals. Here we report a real-space investigation of the phase behaviour of a colloidal monolayer interacting with a quasicrystalline decagonal substrate created by interfering five laser beams. We find a pseudomorphic phase that shows both crystalline and quasicrystalline structural properties. It can be described by an archimedean-like tiling consisting of alternating rows of square and triangular tiles. The calculated diffraction pattern of this phase is in agreement with recent observations of copper adsorbed on icosahedral Al(70)Pd(21)Mn(9) surfaces. In addition to establishing a link between archimedean tilings and quasicrystals, our experiments allow us to investigate in real space how single-element monolayers can form commensurate structures on quasicrystalline surfaces.     

Unravelling the dynamics of RNA degradation by ribonuclease II and its RNA-bound complex

RNA degradation is a determining factor in the control of gene expression. The maturation, turnover and quality control of RNA is performed by many different classes of ribonucleases. Ribonuclease II (RNase II) is a major exoribonuclease that intervenes in all of these fundamental processes; it can act independently or as a component of the exosome, an essential RNA-degrading multiprotein complex. RNase II-like enzymes are found in all three kingdoms of life, but there are no structural data for any of the proteins of this family. Here we report the X-ray crystallographic structures of both the ligand-free (at 2.44 A resolution) and RNA-bound (at 2.74 A resolution) forms of Escherichia coli RNase II. In contrast to sequence predictions, the structures show that RNase II is organized into four domains: two cold-shock domains, one RNB catalytic domain, which has an unprecedented alphabeta-fold, and one S1 domain. The enzyme establishes contacts with RNA in two distinct regions, the 'anchor' and the 'catalytic' regions, which act synergistically to provide catalysis. The active site is buried within the RNB catalytic domain, in a pocket formed by four conserved sequence motifs. The structure shows that the catalytic pocket is only accessible to single-stranded RNA, and explains the specificity for RNA versus DNA cleavage. It also explains the dynamic mechanism of RNA degradation by providing the structural basis for RNA translocation and enzyme processivity. We propose a reaction mechanism for exonucleolytic RNA degradation involving key conserved residues. Our three-dimensional model corroborates all existing biochemical data for RNase II, and elucidates the general basis for RNA degradation. Moreover, it reveals important structural features that can be extrapolated to other members of this family.     

Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction

CD8+ T cells have a crucial role in resistance to pathogens and can kill malignant cells; however, some critical functions of these lymphocytes depend on helper activity provided by a distinct population of CD4+ T cells. Cooperation between these lymphocyte subsets involves recognition of antigens co-presented by the same dendritic cell, but the frequencies of such antigen-bearing cells early in an infection and of the relevant naive T cells are both low. This suggests that an active mechanism facilitates the necessary cell-cell associations. Here we demonstrate that after immunization but before antigen recognition, naive CD8+ T cells in immunogen-draining lymph nodes upregulate the chemokine receptor CCR5, permitting these cells to be attracted to sites of antigen-specific dendritic cell-CD4+ T cell interaction where the cognate chemokines CCL3 and CCL4 (also known as MIP-1alpha and MIP-1beta) are produced. Interference with this actively guided recruitment markedly reduces the ability of CD4+ T cells to promote memory CD8+ T-cell generation, indicating that an orchestrated series of differentiation events drives nonrandom cell-cell interactions within lymph nodes, optimizing CD8+ T-cell immune responses involving the few antigen-specific precursors present in the naive repertoire.     

A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3

To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 x 10(-13) overall; P = 6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P = 3.3 x 10(-18) overall; P = 9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.     

Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21

In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.