A key role for transmembrane prolines in calcitonin receptor-like receptor agonist binding and signalling:implications for family B G-protein-coupled receptors

Calcitonin receptor like-receptor is a family B G-protein coupled receptor (GPCR). It requires receptor activity modifying protein (RAMP) 1 to give a calcitonin gene-related peptide (CGRP) receptor. Little is known of how members of this receptor family function. Proline residues often form important kinks in alpha-helices. Therefore, all proline residues within the transmembrane helices of the receptor (Pro241, Pro244 in helix 4, Pro275 in helix 5, Pro321 and Pro331 in helix 6) were mutated to alanine. Pro241 Pro275, and Pro321 are highly conserved throughout all family B GPCRs. The binding of CGRP and its ability to stimulate cAMP production were investigated in mutant and wild-type receptors after transient transfection into COS-7 cells with RAMP1. The P321A mutation significantly decreased the pEC(50) for CGRP and reduced its affinity but did not change cell-surface expression. Antagonist binding [CGRP(8-37) and 1-piperidinecarboxamide N-[2-[[5amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3 5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quina zolinyl) (BIBN4096BS)] was little altered by the mutation. Adrenomedullin-mediated signaling was disrupted when P321A was coexpressed with RAMP1, RAMP2, or RAMP3. The P331A mutant produced a moderate reduction in CGRP binding and receptor activation. Mutation of the other residues had no effect on receptor function. Thus, Pro321 and Pro331 are required for agonist binding and receptor activation. Modeling suggested that Pro321 induces a bend in helix 6, bringing its C terminus near that of helix 3, as seen in many family A GPCRs. This is abolished in P321A. P321A-I325P predicted to restore this conformation, showed wild-type activation. Modeling can also rationalize the effects of transmembrane proline mutants previously reported for another family B GPCR, the VPAC(1) receptor.

Bit-error rate performance of 20 Gbit/s WDM RZ-DPSK non-slope matched submarine transmission systems

Applying direct error counting, we assess the performance of 20 Gbit/s wavelength-division multiplexing return-to-zero differential phase-shift keying (RZ-DPSK) transmission at 0.4 bit/(s Hz) spectral efficiency for application on installed non-zero dispersion-shifted fibre based transoceanic submarine systems. The impact of the pulse duty cycle on the system performance is investigated and the reliability of the existing theoretical approaches to the BER estimation for the RZ-DPSK format is discussed.

Figurationen:Zum lyrischen Werk von W.G. Sebald

W. G. Sebald gilt heute als der vielleicht bedeutendste deutschsprachige Autor des späten 20. Jahrhunderts. Seine Prosawerke haben eine kaum mehr überrschaubare Zahl von Deutungen und Kommentaren in Gang gesetzt. Wenig bekannt hingegen sind seine Gedichte, die im Verlauf von vier Jahrzehnten entstanden und zumeist posthum publiziert wurden. Diese Studie des Sebald-Schülers Uwe Schütte vermittelt einen kenntnisreichen Einblick in das poeti­schen Gesamtwerk – von den Jugendgedichten bis zu den enigmatischen Mikropoemen, an denen Sebald unmittelbar vor seinem Tod arbeitete – wobei auch unbekannte Texte aus dem Nachlass analysiert werden. »Figurationen« macht es möglich, W. G. Sebald als Lyriker (neu) zu entdecken.

Strain-facilitated process for the lift-off of a Si layer of less than 20 nm thickness

We report a process for the lift-off of an ultrathin Si layer. By plasma hydrogenation of a molecular-beam-epitaxy-grown heterostructure of SiSb-doped-SiSi, ultrashallow cracking is controlled to occur at the depth of the Sb-doped layer. Prior to hydrogenation, an oxygen plasma treatment is used to induce the formation of a thin oxide layer on the surface of the heterostructure. Chemical etching of the surface oxide layer after hydrogenation further thins the thickness of the separated Si layer to be only 15 nm. Mechanisms of hydrogen trapping and strain-facilitated cracking are discussed. © 2005 American Institute of Physics.

Interventionen:Literaturkritik als Widerspruch bei W. G. Sebald

"Ich habe einen Horror vor allen billigen Formen der Fiktionalisierung. Mein Medium ist die Prosa, nicht der Roman", begründet W. G. Sebald seine Neigung zum essayistischen Schreiben. Und eben diese Erzählprosa W. G. Sebalds bildet den Stoff, auf dem Uwe Schüttes eindrückliche und kritische Beobachtungen zum biografischen, literaturwissenschaftlichen und literarischen Werdegang des Autors von "Austerlitz" fußen. W. G. Sebald ist einer der anerkanntesten und zugleich umstrittensten Schriftsteller der deutschen Literatur des späten 20. Jahrhunderts. Sein vielgerühmtes literarisches Werk ruht auf einem Fundament, das größtenteils kaum bekannt ist, nämlich die im Verlauf von rund 30 Jahren entstandenen kritischen Schriften. "Interventionen" bietet erstmals einen so tiefschürfenden wie umfassenden Überblick über die Literaturkritik Sebalds unter Einbezug zuvor unveröffentlichter Archivdokumente. Uwe Schütte, der bei Sebald promoviert hat, legt anschaulich dar, wie sich Sebalds eigenwillige Literaturkritik – von der Magisterarbeit über Carl Sternheim bis zum polemischen Essay "Luftkrieg und Literatur" – entwickelt hat. Seine Studie skizziert damit die intellektuelle Biografie des vom Allgäu in die Provinz East Anglias entlaufenen Germanisten. Vor allem aber zeichnet "Interventionen" nach, wie Sebald im kritischen Widerspruch zu Germanistik und deutscher Nachkriegsliteratur selbst zum Schriftsteller wurde. Der Autor Uwe Schütte, geb. 1967, promovierte 1997 bei W. G. Sebald an der University of East Anglia und ist Reader in German an der Aston University in Birmingham, England.

Bit-error rate performance of 20 Gbit/s WDM RZ-DPSK non-slope matched submarine transmission systems

Applying direct error counting, we assess the performance of 20 Gbit/s wavelength-division multiplexing return-to-zero differential phase-shift keying (RZ-DPSK) transmission at 0.4 bit/(s Hz) spectral efficiency for application on installed non-zero dispersion-shifted fibre based transoceanic submarine systems. The impact of the pulse duty cycle on the system performance is investigated and the reliability of the existing theoretical approaches to the BER estimation for the RZ-DPSK format is discussed.

Progress toward 100-G digital coherent pluggables using InP-based photonics

A new generation of high-capacity WDM systems with extremely robust performance has been enabled by coherent transmission and digital signal processing. To facilitate widespread deployment of this technology, particularly in the metro space, new photonic components and subsystems are being developed to support cost-effective, compact, and scalable transceivers. We briefly review the recent progress in InP-based photonic components, and report numerical simulation results of an InP-based transceiver comprising a dual-polarization I/Q modulator and a commercial DSP ASIC. Predicted performance penalties due to the nonlinear response, lower bandwidth, and finite extinction ratio of these transceivers are less than 1 and 2 dB for 100-G PM-QPSK and 200-G PM-16QAM, respectively. Using the well-established Gaussian-Noise model, estimated system reach of 100-G PM-QPSK is greater than 600 km for typical ROADM-based metro-regional systems with internode losses up to 20 dB. © 1983-2012 IEEE.

Association of SNPs in LCP1 and CTIF with hearing in 11 year old children:findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and the G-EAR consortium

BACKGROUND: The genetic basis of hearing loss in humans is relatively poorly understood. In recent years, experimental approaches including laboratory studies of early onset hearing loss in inbred mouse strains, or proteomic analyses of hair cells or hair bundles, have suggested new candidate molecules involved in hearing function. However, the relevance of these genes/gene products to hearing function in humans remains unknown. We investigated whether single nucleotide polymorphisms (SNPs) in the human orthologues of genes of interest arising from the above-mentioned studies correlate with hearing function in children. METHODS: 577 SNPs from 13 genes were each analysed by linear regression against averaged high (3, 4 and 8 kHz) or low frequency (0.5, 1 and 2 kHz) audiometry data from 4970 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth-cohort at age eleven years. Genes found to contain SNPs with low p-values were then investigated in 3417 adults in the G-EAR study of hearing. RESULTS: Genotypic data were available in ALSPAC for a total of 577 SNPs from 13 genes of interest. Two SNPs approached sample-wide significance (pre-specified at p = 0.00014): rs12959910 in CBP80/20-dependent translation initiation factor (CTIF) for averaged high frequency hearing (p = 0.00079, β = 0.61 dB per minor allele); and rs10492452 in L-plastin (LCP1) for averaged low frequency hearing (p = 0.00056, β = 0.45 dB). For low frequencies, rs9567638 in LCP1 also enhanced hearing in females (p = 0.0011, β = -1.76 dB; males p = 0.23, β = 0.61 dB, likelihood-ratio test p = 0.006). SNPs in LCP1 and CTIF were then examined against low and high frequency hearing data for adults in G-EAR. Although the ALSPAC results were not replicated, a SNP in LCP1, rs17601960, is in strong LD with rs9967638, and was associated with enhanced low frequency hearing in adult females in G-EAR (p = 0.00084). CONCLUSIONS: There was evidence to suggest that multiple SNPs in CTIF may contribute a small detrimental effect to hearing, and that a sex-specific locus in LCP1 is protective of hearing. No individual SNPs reached sample-wide significance in both ALSPAC and G-EAR. This is the first report of a possible association between LCP1 and hearing function.