Tunneling Between Two-Dimensional Electron Gases in a Strong Magnetic Field

We have measured the tunneling between two two-dimensional electron gases at high magnetic fields $B$, when the carrier densities of the two electron layers are matched. For filling factors $\nu<1$, there is a gap in the current-voltage characteristics centered about $V=0$, followed by a tunneling peak at $\sim 6$~mV. Both features have been observed before and have been attributed to electron-electron interactions within a layer. We have measured high field tunneling peak positions and fitted gap parameters that are proportional to $B$, and independent of the carrier densities of the two layers. This suggests a different origin for the gap to that proposed by current theories, which predict a $\sqrt{B}$ dependence.Comment: 9 pages, cond-mat/yymmnn

Piano Course: Grade 7, Compositions

A Lesson Book for the Piano Courses administered by the Sherwood Music School\u27s Extension Division. Grade 7, Graduate A: Compositions, number 701 through 760https://digitalcommons.colum.edu/piano/1022/thumbnail.jp

Mutational analysis of human CEACAM1: the potential of receptor polymorphism in increasing host susceptibility to bacterial infection

A common overlapping site on the N-terminal IgV-like domain of human carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) is targeted by several important human respiratory pathogens. These include Neisseria meningitidis (Nm) and Haemophilus influenzae (Hi) that can cause disseminated or persistent localized infections. To define the precise structural features that determine the binding of distinct pathogens with CEACAMs, we have undertaken molecular modelling and mutation of the receptor molecules at previously implicated key target residues required for bacterial binding. These include Ser-32, Tyr-34, Val-39, Gln-44 and Gln-89, in addition to Ile-91, the primary docking site for the pathogens. Most, but not all, of these residues located adjacent to each other in a previous N-domain model of human CEACAM1, which was based on REI, CD2 and CD4. In the current studies, we have refined this model based on the mouse CEACAM1 crystal structure, and observe that all of the above residues form an exposed continuous binding region on the N-domain. Examination of the model also suggested that substitution of two of these residues 34 and 89 could affect the accessibility of Ile-91 for ligand binding. By introducing selected mutations at the positions 91, 34 and 89, we confirmed the primary importance of Ile-91 in all bacterial binding to CEACAM1 despite the inter- and intraspecies structural differences between the bacterial CEACAM-binding ligands. The studies further indicated that the efficiency of binding was significantly enhanced for specific strains by mutations such as Y34F and Q89N, which also altered the hierarchy of Nm versus Hi strain binding. These studies imply that distinct polymorphisms in human epithelial CEACAMs have the potential to decrease or increase the risk of infection by the receptor-targeting pathogens

Tunneling Between Parallel Two-Dimensional Electron Gases

The tunneling between two parallel two-dimensional electron gases has been investigated as a function of temperature $T$, carrier density $n$, and the applied perpendicular magnetic field $B$. In zero magnetic field the equilibrium resonant lineshape is Lorentzian, reflecting the Lorentzian form of the spectral functions within each layer. From the width of the tunneling resonance the lifetime of the electrons within a 2DEG has been measured as a function of $n$ and $T$, giving information about the density dependence of the electron-impurity scattering and the temperature dependence of the electron-electron scattering. In a magnetic field there is a general suppression of equilibrium tunneling for fields above $B=0.6$ T. A gap in the tunneling density of states has been measured over a wide range of magnetic fields and filling factors, and various theoretical predictions have been examined. In a strong magnetic field, when there is only one partially filled Landau level in each layer, the temperature dependence of the conductance characteristics has been modeled with a double-Gaussian spectral density.Comment: LaTeX requires REVTeX macros. Eighteen pages. Fourteen postscript figures are included. (All figures have been bitmapped to save space. The original can be requested by email from [email protected]). Accepted for publication in Phys. Rev.

Neisseria meningitidis Opc invasin binds to the cytoskeletal protein α-actinin

Neisseria meningitidis Opc protein is an effective invasin for human endothelial cells. We have investigated novel human endothelial receptors targeted by Opc and observed that Opc-expressing bacteria interacted with a 100 kDa protein in whole-cell lysates of human endothelial and epithelial cells. The identity of the protein was established as α-actinin by mass spectrometry. Opc expression was essential for the recognition of α-actinin whether provided in a purified form or in cell extracts. The interaction of the two proteins did not involve intermediate molecules. As there was no demonstrable expression of α-actinin on the surfaces of any of the eight cell lines studied, the likelihood of the interactions after meningococcal internalization was examined. Confocal imaging demonstrated considerable colocalization of N. meningitidis with α-actinin especially after a prolonged period of internalization. This may imply that bacteria and α-actinin initially occur in separate compartments and co-compartmentalization occurs progressively over the 8 h infection period used. In conclusion, these studies have identified a novel and an intracellular target for the N. meningitidis Opc invasin. Since α-actinin is a modulator of a variety of signalling pathways and of cytoskeletal functions, its targeting by Opc may enable bacteria to survive/translocate across endothelial barriers

Neisseria meningitidis Opc Invasin Binds to the Sulphated Tyrosines of Activated Vitronectin to Attach to and Invade Human Brain Endothelial Cells

The host vasculature is believed to constitute the principal route of dissemination of Neisseria meningitidis (Nm) throughout the body, resulting in septicaemia and meningitis in susceptible humans. In vitro, the Nm outer membrane protein Opc can enhance cellular entry and exit, utilising serum factors to anchor to endothelial integrins; but the mechanisms of binding to serum factors are poorly characterised. This study demonstrates that Nm Opc expressed in acapsulate as well as capsulate bacteria can increase human brain endothelial cell line (HBMEC) adhesion and entry by first binding to serum vitronectin and, to a lesser extent, fibronectin. This study also demonstrates that Opc binds preferentially to the activated form of human vitronectin, but not to native vitronectin unless the latter is treated to relax its closed conformation. The direct binding of vitronectin occurs at its Connecting Region (CR) requiring sulphated tyrosines Y56 and Y59. Accordingly, Opc/vitronectin interaction could be inhibited with a conformation-dependent monoclonal antibody 8E6 that targets the sulphotyrosines, and with synthetic sulphated (but not phosphorylated or unmodified) peptides spanning the vitronectin residues 43–68. Most importantly, the 26-mer sulphated peptide bearing the cell-binding domain 45RGD47 was sufficient for efficient meningococcal invasion of HBMECs. To our knowledge, this is the first study describing the binding of a bacterial adhesin to sulphated tyrosines of the host receptor. Our data also show that a single region of Opc is likely to interact with the sulphated regions of both vitronectin and of heparin. As such, in the absence of heparin, Opc-expressing Nm interact directly at the CR but when precoated with heparin, they bind via heparin to the heparin-binding domain of the activated vitronectin, although with a lower affinity than at the CR. Such redundancy suggests the importance of Opc/vitronectin interaction in meningococcal pathogenesis and may enable the bacterium to harness the benefits of the physiological processes in which the host effector molecule participates

Bacterial phase variation associated with repetitive DNA

Phase variation is mechanism of phenotypic switching used by many pathogenic bacterial species. This thesis describes work on three aspects of phase variation. Mathematical models are described which can be used to determine the rate of phase variation and subsequently the influence of variation rate and fitness differences associated with the altered phenotype on population structure. An approach to whole genome analysis has been developed which has been used to identify putative phase variable contingency genes in H. pylori, T. pallidum and N. meningitidis. This has identified many new contingency genes likely to be involved in host - bacterium and bacterium population interactions. Finally, a detailed molecular investigation of the promoter of the phase variable opc gene of N. meningitidis is presented. In this it is shown that the promoter located homopolymeric tract controls transcription by affecting the relative spacing and facing of promoter components, that this determines RNA polymerase binding to the promoter, and that this interaction involves direct contact of the α-subunit of RNA polymerase with the promoter. In addition it is shown that transcription is dependent upon an IHF consensus sequence in the opc promoter

The skinny on CCN2

The CCN family of matricellular proteins directly or indirectly affects development and differentiation. A recent report written by Tan and colleagues (Am J Physiol Cell Physiol 295: C740–C751 2008) shows that CCN2 inhibits adipocyte differentiation. This commentary summarizes these observations

A proposal on cancer data quality checks: one common procedure for European cancer registries (version 1.1)

During the last two years the European Network of Cancer Registries (ENCR) and the European Commission's Joint Research Centre (JRC) have been working in preparing the 2015 ENCR-JRC call for data and developing the JRC-ENCR Quality Check software (QCS). The JRC Technical Report ‘A proposal on cancer data quality checks: one common procedure for European cancer registries’, published in November 2014, was the basis for preparing the 2015 data call protocol and developing the QCS. Nevertheless, there are some small differences in variables considered and their respective formats between the 2014 JRC Technical Report and the 2015 call for data protocol. In addition to that, quality checks for multiple primary tumours have been included in the QCS. Moreover, a few errors in the 2014 report were identified and were corrected in the present document. The objective of this addendum is to update version 1.0 of the JRC Technical Report ‘A proposal on cancer data quality checks: one common procedure for European cancer registries’ according to the 2015 ENCR-JRC call for data protocol, the QCS latest version and the feedback obtained from the users.JRC.F.1-Health in Societ