Peptide DV-28 amide: Prototype of a novel class of bradykinin receptor antagonist isolated from the defensive skin secretion of bombinid toads

Kinestatin, isolated from the skin of the Chinese toad, Bombina maxima, was the first bradykinin B2 receptor antagonist identified in amphibians. Molecular cloning established that it is co-encoded with the bradykinin-related peptide, maximakinin, within one of several skin kininogens. To examine other species within the genus Bombina for the presence of structural homologues of kinestatin, we subjected skin secretion of the toad, Bombina orientalis, to HPLC fractionation with subsequent bioassay of fractions for antagonism of bradykinin activity using an isolated rat tail artery smooth muscle preparation. A single fraction was located that inhibited bradykinin-induced relaxation of rat arterial smooth muscle and MALDI-TOF analysis of this fraction revealed that it contained a single peptide of molecular mass 3198.5 Da. Further primary structural analysis of this peptide showed that it was a 28-mer with an N-terminal Asp (D) residue and a C-terminal Val (V) residue that was amidated. The peptide was named DV-28 amide in accordance with these primary structural attributes. Synthetic DV-28 amide replicated the observed bradykinin antagonistic effect within the smooth muscle bioassay in a dose-dependent manner. In addition, it was observed to inhibit the proliferation of human microvessel endothelial cells (HMECs) as assessed by MTT assay. Bioinformatic analysis revealed that DV-28 amide was, like kinestatin, co-encoded with a bradykinin receptor agonist on one of two skin kininogens identified in B. orientalis. DV-28 amide thus represents a novel class of bradykinin antagonist from skin secretions of bombinid toads that appear to be a rich source of such novel peptides.

Digital Baseband Predistortion Based Linearized Broadband Inverse Class-E Power Amplifier

A newly introduced inverse class-E power amplifier (PA) was designed, simulated, fabricated, and characterized. The PA operated at 2.26 GHz and delivered 20.4-dBm output power with peak drain efficiency (DE) of 65% and power gain of 12 dB. Broadband performance was achieved across a 300-Mitz bandwidth with DE of better than 50% and 1-dB output-power flatness. The concept of enhanced injection predistortion with a capability to selectively suppress unwanted sub-frequency components and hence suitable for memory effects minimization is described coupled with a new technique that facilitates an accurate measurement of the phase of the third-order intermodulation (IM3) products. A robust iterative computational algorithm proposed in this paper dispenses with the need for manual tuning of amplitude and phase of the IM3 injected signals as commonly employed in the previous publications. The constructed inverse class-E PA was subjected to a nonconstant envelope 16 quadrature amplitude modulation signal and was linearized using combined lookup table (LUT) and enhanced injection technique from which superior properties from each technique can be simultaneously adopted. The proposed method resulted in 0.7% measured error vector magnitude (in rms) and 34-dB adjacent channel leakage power ratio improvement, which was 10 dB better than that achieved using the LUT predistortion alone.

Hybridization of a class of "second order" models of traffic flow

Despite the simultaneous progress of traffic modelling both on the macroscopic and microscopic front, recent works [E. Bourrel, J.B. Lessort, Mixing micro and macro representation of traffic flow: a hybrid model based on the LWR theory, Transport. Res. Rec. 1852 (2003) 193–200; D. Helbing, M. Treiber, Critical discussion of “synchronized flow”, Coop. Transport. Dyn. 1 (2002) 2.1–2.24; A. Hennecke, M. Treiber, D. Helbing, Macroscopic simulations of open systems and micro–macro link, in: D. Helbing, H.J. Herrmann, M. Schreckenberg, D.E. Wolf (Eds.), Traffic and Granular Flow ’99, Springer, Berlin, 2000, pp. 383–388] highlighted that one of the most promising way to simulate efficiently traffic flow on large road networks is a clever combination of both traffic representations: the hybrid modelling. Our focus in this paper is to propose two hybrid models for which the macroscopic (resp. mesoscopic) part is based on a class of second order model [A. Aw, M. Rascle, Resurection of second order models of traffic flow?, SIAM J. Appl. Math. 60 (2000) 916–938] whereas the microscopic part is a Follow-the Leader type model [D.C. Gazis, R. Herman, R.W. Rothery, Nonlinear follow-the-leader models of traffic flow, Oper. Res. 9 (1961) 545–567; R. Herman, I. Prigogine, Kinetic Theory of Vehicular Traffic, American Elsevier, New York, 1971]. For the first hybrid model, we define precisely the translation of boundary conditions at interfaces and for the second one we explain the synchronization processes. Furthermore, through some numerical simulations we show that the waves propagation is not disturbed and the mass is accurately conserved when passing from one traffic representation to another.

Power-Combining Class-E Amplifier With Finite Choke

A recently introduced power-combining scheme for a Class-E amplifier is, for the first time, experimentally validated in this paper. A small value choke of 2.2 nH was used to substitute for the massive dc-feed inductance required in the classic Class-E circuit. The power-combining amplifier presented, which operates from a 3.2-V dc supply voltage, is shown to be able to deliver a 24-dBm output power and a 9.5-dB gain, with 64% drain efficiency and 57% power-added efficiency at 2.4 GHz. The power amplifier exhibits a 350-MHz bandwidth within which a drain efficiency that is better than 60% and an output power that is higher than 22 dBm were measured. In addition, by adopting three-harmonic termination strategy, excellent second-and third-harmonic suppression levels of 50 and 46 dBc, respectively, were obtained. The complete design cycle from analysis through fabrication to characterization is explained. © 2010 IEEE.

Will attracting the creative class boost economic growth in old industrial regions? A case study of Scotland

Attracting in-migration of the creative class has been argued by Florida (2002) to be a route to higher economic growth in the era of the knowledge economy. This paper critically evaluates this proposition in relation to old industrial regions using the example of Scotland. The paper presents an assessment of, in the first instance, to what extent there is a shortage of skilled, talented and entrepreneurial individuals and, in the second instance, whether a talent attraction strategy alone can hope to attract such people to Scotland. It is proposed that for most migrants the availability of appropriate economic opportunities is a prerequisite for mobility. However, despite uncertain evidence that place attractiveness is a catalyst to mobility among the so-called creative class, this is not a reason for dismissing talent attraction programmes. Instead it is argued that talent attraction programmes have the potential to contribute to old industrial economies, but their success will be greatest when talent attraction is carefully targeted and based on economic realities rather than the marketing of ethereal conceptions of place attractiveness.

Long-term occlusal and soft-tissue profile outcomes after treatment of Class II Division 1 malocclusion with fixed appliances

Introduction: Our objective was to determine which factors were predictive of good long-term outcomes after fixed appliance treatment of Class II Division 1 malocclusion. Methods: Two hundred seven patients with Class II Division 1 malocclusion were examined in early adulthood at a mean of 4.6 years after treatment with fixed appliances. The peer assessment rating index was used to evaluate dental alignment and occlusal relationships. The soft-tissue profile was assessed with the Holdaway angle. Results: Logistic regression identified 3 pretreatment variables that were predictive of a good facial profile (Holdaway angle) at recall: the lower lip to E-plane distance (P

Limnonectins: A new class of antimicrobial peptides from the skin secretion of the Fujian large-headed frog (Limnonectes fujianensis)

Amphibian skin secretions are rich sources of biologically-active peptides with antimicrobial peptides predominating in many species. Several studies involving molecular cloning of biosynthetic precursor-encoding cDNAs from skin or skin secretions have revealed that these exhibit highly-conserved domain architectures with an unusually high degree of conserved nucleotide and resultant amino acid sequences within the signal peptides. This high degree of nucleotide sequence conservation has permitted the design of primers complementary to such sites facilitating “shotgun” cloning of skin or skin secretion-derived cDNA libraries from hitherto unstudied species. Here we have used such an approach using a skin secretion-derived cDNA library from an unstudied species of Chinese frog – the Fujian large-headed frog, Limnonectes fujianensis – and have discovered two 16-mer peptides of novel primary structures, named limnonectin-1Fa (SFPFFPPGICKRLKRC) and limnonectin-1Fb (SFHVFPPWMCKSLKKC), that represent the prototypes of a new class of amphibian skin antimicrobial peptide. Unusually these limnonectins display activity only against a Gram-negative bacterium (MICs of 35 and 70 µM) and are devoid of haemolytic activity at concentrations up to 160 µM. Thus the “shotgun” cloning approach described can exploit the unusually high degree of nucleotide conservation in signal peptide-encoding domains of amphibian defensive skin secretion peptide precursor-encoding cDNAs to rapidly expedite the discovery of novel and functional defensive peptides in a manner that circumvents specimen sacrifice without compromising robustness of data

Biaryl polyamides as a new class of DNA quadruplex-binding ligands

We report a novel class of biaryl polyamides highly selective for G-quadruplex DNA, and with significant cytotoxicity in several cancer cell lines; they form planar U-shaped structures that match the surface area dimensions of a terminal G-quartet in quadruplex structures rather than the grooves of duplex DNA.