Mutations within subdomain II of the extracellular region of epidermal growth factor receptor selectively alter TGF alpha binding

The interactions of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) with the epidermal growth factor receptor (EGFR) were examined by insertion mutagenesis of the receptor. Seventeen insertions were made throughout a construct containing only the extracellular domain. This truncated receptor (sEGFR) was secreted and had a dissociation constant similar to that of the full-length solubilized receptor. Receptors with insertions within subdomain III were not secreted. Two receptors with insertions at positions 291 and 474, which border subdomain III, have significantly decreased binding to both EGF and TGF alpha relative to wild type. This confirms previous work demonstrating that subdomain III forms the primary binding site for EGF and TGF alpha. Four of the mutants within subdomain II had a decreased binding to TGF alpha relative to wild type, but had wild type binding to EGF. These results suggest that a region within subdomain II may selectively regulate the binding of TGF alpha. Two receptors which contained insertions within subdomains II and IV, approximately equidistant from the center of subdomain III, bound twofold more ligand molecules than wild type receptor, with an affinity similar to that of wild type receptor. These findings suggest that insertion at these positions allows the access of more than one ligand molecule to the binding site.

Discrimination of honey of different floral origins by a combination of various chemical parameters

Abstract Honey is a high value food commodity with recognized nutraceutical properties. A primary driver of the value of honey is its floral origin. The feasibility of applying multivariate data analysis to various chemical parameters for the discrimination of honeys was explored. This approach was applied to four authentic honeys with different floral origins (rata, kamahi, clover and manuka) obtained from producers in New Zealand. Results from elemental profiling, stable isotope analysis, metabolomics (UPLC-QToF MS), and NIR, FT-IR, and Raman spectroscopic fingerprinting were analyzed. Orthogonal partial least square discriminant analysis (OPLS-DA) was used to determine which technique or combination of techniques provided the best classification and prediction abilities. Good prediction values were achieved using metabolite data (for all four honeys, Q² = 0.52; for manuka and clover, Q² = 0.76) and the trace element/isotopic data (for manuka and clover, Q² = 0.65), while the other chemical parameters showed promise when combined (for manuka and clover, Q² = 0.43).

Optimisation of source/drain extension region profile for suppression of short channel effects in sub-50 nm DG SOI MOSFETs with high- k gate dielectrics

Novel technology dependent scaling parameters i.e. spacer to gradient ratio and effective channel length (Leff) are proposed for source/drain engineered DG MOSFET, and their significance in minimizing short channel effects (SCES) in high-k gate dielectrics is discussed in detail. Results show that a high-k dielectric should be associated with a higher spacer to gradient ratio to minimise SCEs The analytical model agrees with simulated data over the entire range of spacer widths, doping gradients, high-k gate dielectrics and effective channel lengths.

The extreme-ultraviolet structure and properties of a newly emerged active region

The structure and properties of a newly emerged solar active region (NOAA Active Region 7985) are discussed using the Coronal Diagnostic Spectrometer (CDS) and the Extreme- Ultraviolet Imaging Telescope (EIT) on board the Solar and Heliospheric Observatory. CDS obtained high-resolution EUV spectra in the 308-381 Angstrom and 513-633 Angstrom wavelength ranges, while EIT recorded full-disk EUV images in the He II (304 Angstrom), Fe IX/X (171 Angstrom), Fe xii (195 Angstrom), and Fe XV (284 Angstrom) bandpasses. Electron density measurements from Si rx, Si X, Fe xii, Fe XIII, and Fe xiv line ratios indicate that the region consists of a central high- density core with peak densities of the order of 1.2 x 10(10) cm(-3), which decrease monotonically to similar to5.0 X 10(8) cm(-3) at the active region boundary. The derived electron densities also vary systematically with temperature. Electron pressures as a function of both active region position and temperature were estimated using the derived electron densities and ion formation temperatures, and the constant pressure assumption was found to be an unrealistic simplification. Indeed, the active region is found to have a high-pressure core (1.3 x 10(16) cm(-3) K) that falls to 6.0 x 10(14) cm(-3) K just outside the region. CDS line ratios from different ionization stages of iron, specifically Fe xvi (335.4 Angstrom) and Fe xiv (334.4 Angstrom), were used to diagnose plasma temperatures within the active region. Using this method, peak temperatures of 2.1 x 10(6) K were identified. This is in good agreement with electron temperatures derived using EIT filter ratios and the two-temperature model of Zhang et al. The high- temperature emission is confined to the active region core, while emission from cooler (1-1.6) x 10(6) K lines originates in a system of loops visible in EIT 171 and 195 X images. Finally, the three-dimensional geometry of the active region is investigated using potential field extrapolations from a Kitt Peak magnetogram. The combination of EUV and magnetic field extrapolations extends the "core-halo" picture of active region structure to one in which the core is composed of a number of compact coronal loops that confine the hot, dense, high- pressure core plasma while the halo emission emerges from a system of cooler and more extended loops.

Getting off the escalator? A study of Scots out-migration from a global city region

Something new is happening to reverse the historical trend of skilled Scots moving to London for career progression. The Scottish population of London and the South East is falling and this despite Scots enjoying continued occupational success within the South East labour market. The authors ask why Scots are leaving the UK's main escalator region and then investigate how these migration changes can best be theorised relative to literature on the mobility of the 'new service class'. Building on Fielding's escalator region hypothesis, the authors report on recent research on longer distance flows out of the UK's main escalator region. They advance the critique of the escalator region hypothesis set out by Findlay et al and ask why people would leave a global city offering good opportunities for occupational mobility. Demographic regime change provides only a partial answer. Other explanations can be found in the changing mobilities of the new service class as they engage in what Smith has defined as 'translocal' and 'transnational' urbanism. The authors argue that Scotland's changing relationship with London and the South East may be representative of a wider set of changes in migration linkages between regional economies and global cities.

Promoter region of the Escherichia coli O7-specific lipopolysaccharide gene cluster:structural and functional characterization of an upstream untranslated mRNA sequence

We report the identification of the promoter region of the Escherichia coli O7-specific lipopolysaccharide (LPS) gene cluster (wbEcO7). Typical -10 and -35 sequences were found to be located in the intervening region between galF and rlmB, the first gene of the wbEcO7 cluster. Data from RNase protection experiments revealed the existence of an untranslated leader mRNA segment of 173 bp, including the JUMPStart and two ops sequences. We characterized the structure of this leader mRNA by using the program Mfold and a combination of nested and internal deletions transcriptionally fused to a promoterless lac operon. Our results indicated that the leader mRNA may fold into a series of complex stem-loop structures, one of which includes the JUMPStart element. We have also found that one of the ops sequences resides on the predicted stem and the other resides on the loop region, and we confirmed that these sequences are essential for the RfaH-mediated regulation of the O polysaccharide cluster. A very similar stem-loop structure could be predicted in the promoter region of the LPS core operon encoding the waaQGPSBIJYZK genes. We observed another predicted stem-loop, located immediately downstream from the wbEcO7 transcription initiation site, which appeared to be involved in premature termination of transcription. This putative stem-loop is common to many other O polysaccharide gene clusters but is not present in core oligosaccharide genes. wbEcO7-lac transcriptional fusions in single copy numbers were also used to determine the effects of various environmental cues in the transcriptional regulation of O polysaccharide synthesis. No effects were detected with temperature, osmolarity, Mg2+ concentration, and drugs inducing changes in DNA supercoiling. We therefore conclude that the wbEcO7 promoter activity may be constitutive and that regulation takes place at the level of elongation of the mRNA in a RfaH-mediated manner.