A novel diagnostic test detects a low frequency of the hemicentin Gln5345Arg variant among Northern Irish age related macular degeneration patients.

Purpose: Age related macular degeneration (AMD) is a common cause of severe vision loss. Identification of genes involved in AMD will facilitate early detection and ultimately help to identify pathways for treatment for this disorder. The A16,263G mutation in the HEMICENTIN-1 gene produces a non-conservative substitution of arginine for glutamine at codon 5345 which has been implicated in familial AMD. The aim of this study is to develop a rapid diagnostic assay for the detection of this mutation and to evaluate its frequency in a sample of AMD patients. Methods: A primer probe set was designed from exon 104 of the HEMICENTIN-1 gene to differentiate between mutant and wild type alleles. A region spanning the mutation was amplified by PCR using a LightCycler (Roche Diagnostic). The mutation was then detected by melt curve analysis of the hybrid formed between the PCR product and a specific fluorescent probe. The frequency of the mutation within the Northern Ireland population was evaluated by assaying 508 affected AMD patients, 25 possibly affected and 163 controls. Results: This assay clearly discriminates between the A16,263G mutant and wild type HEMICENTIN-1 alleles. The wild type sequence has a single base mismatch with the probe which decreases the stability of the hybrid, resulting in a lower TM (TM=51.27 °C) than that observed for the perfectly matched mutant allele (TM=59.9 °C). The mutant allele was detected in only one of the 696 subjects, an affected AMD patient. Conclusions: We describe a rapid assay for the genotyping of the Gln5345Arg mutation using real-time fluorescence PCR to facilitate rapid processing of samples through combined amplification and detection steps. These characteristics are suitable for a clinical setting where high throughput diagnostic procedures are required. The frequency of this mutation within the Northern Ireland population has been estimated at 0.2%, concurring with previous findings that this mutation is a rare variant associated with AMD. A rapid diagnostic assay will facilitate a reliable and convenient evaluation of the frequency of the Gln5345Arg mutation and its association with AMD within other populations.

Single-ionization of helium at Ti:sapphire wavelengths: rates and scaling laws

We present a numerical and theoretical study of intense-field single-electron ionization of helium at 390 nm and 780 nm. Accurate ionization rates (over an intensity range of (0.175-34) X10^14 W/ cm^2 at 390 nm, and (0.275 - 14.4) X 10^14 W /cm^2 at 780 nm) are obtained from full-dimensionality integrations of the time-dependent helium-laser Schroedinger equation. We show that the power law of lowest order perturbation theory, modified with a ponderomotive-shifted ionization potential, is capable of modelling the ionization rates over an intensity range that extends up to two orders of magnitude higher than that applicable to perturbation theory alone. Writing the modified perturbation theory in terms of scaled wavelength and intensity variables, we obtain to first approximation a single ionization law for both the 390 nm and 780 nm cases. To model the data in the high intensity limit as well as in the low, a new function is introduced for the rate. This function has, in part, a resemblance to that derived from tunnelling theory but, importantly, retains the correct frequency-dependence and scaling behaviour derived from the perturbative-like models at lower intensities. Comparison with the predictions of classical ADK tunnelling theory confirms that ADK performs poorly in the frequency and intensity domain treated here.

Single sideband FSS with high image rejection

The design of a quasi-optical single sideband filter, which provides more than 30 dB of isolation between the frequency bands 294-305.5 and 329.5-341.5 GHz in the TM plane at 45 degrees incidence, is described. The structure, which consists of three free-standing arrays of dipole slot elements, generates a bandpass spectral response with an insertion loss below 0.5 dB at resonance. Simulated and measured transmission coefficients in the range 250-400 GHz are shown to be in good agreement.

Idealised operation of zero-voltage-switching series-L/parallel-tuned Class-E power amplifier

An analysis of a modified series-L/parallel-tuned Class-E power amplifier is presented, which includes the effects that a shunt capacitance placed across the switching device will have on Class-E behaviour. In the original series L/parallel-tuned topology in which the output transistor capacitance is not inherently included in the circuit, zero-current switching (ZCS) and zero-current derivative switching (ZCDS) conditions should be applied to obtain optimum Class-E operation. On the other hand, when the output transistor capacitance is incorporated in the circuit, i.e. in the modified series-L/parallel-tuned topology, the ZCS and ZCDS would not give optimum operation and therefore zero-voltage-switching (ZVS) and zero-voltage-derivative switching (ZVDS) conditions should be applied instead. In the modified series-L/parallel-tuned Class-E configuration, the output-device inductance and the output-device output capacitance, both of which can significantly affect the amplifier's performance at microwave frequencies, furnish part, if not all, of the series inductance L and the shunt capacitance COUT, respectively. Further, when compared with the classic shunt-C/series-tuned topology, the proposed Class-E configuration offers some advantages in terms of 44% higher maximum operating frequency (fMAX) and 4% higher power-output capability (PMAX). As in the classic topology, the fMAX of the proposed amplifier circuit is reached when the output-device output capacitance furnishes all of the capacitance COUT, for a given combination of frequency, output power and DC supply voltage. It is also shown that numerical simulations agree well with theoretical predictions.

Even order harmonic Series-L/Parallel-Tuned Class-E frequency multiplier

In this brief, we propose a new Class-E frequency multiplier based on the recently introduced Series-L/Parallel-Tuned Class-E amplifier. The proposed circuit produces even-order output harmonics. Unlike previously reported solutions the proposed circuit can operate under 50% duty ratio which minimizes the conduction losses. The circuit also offers the possibility for increased maximum operating frequency, reduced peak switch voltage, higher load resistance and inherent bond wire absorption; all potentially useful in monolithic microwave integrated circuit implementations. In addition, the circuit topology suggested large transistors with high output capacitances can be deployed. Theoretical design equations are given and the predictions made using these are shown to agree with harmonic balance circuit simulation results.

Design strategies for dual-band class-e power amplifier using composite right/left-handed transmission lines

In this article we propose a technique for dual-band Class-E power amplifier design using composite right/left-handed transmission lines, CRLH TLs. Design equations are presented and design procedures are elaborated. Because of the nonlinear phase dispersion characteristic of CRLH TLs, the single previous attempt at applying this method to dual bond Class-E amplifier design was not sufficient to simultaneously satisfy, the minimum requirement of Class-E impedances at both the fundamental and the second harmonic frequencies. This article rectifies this situation. A design example illustrating the synthesis procedure for a 0.5W-5V dual band Class-E amplifier circuit simultaneously operated at 900 MHz and 2.4 GHz is given and compared with ADS simulation.

Sensitivity characteristics of inverse Class-E power amplifier

In this paper, an analysis is performed in order to determine the effects that variations in circuit component values, frequency, and duty cycle have on the performance of the newly introduced inverse Class-E amplifier. Analysis of the inverse Class-E amplifier under the generalized condition of arbitrary duty cycle is performed and it is shown that the inverse Class-E amplifier is reasonably tolerant to circuit parameter variations. When compared to the conventional Class-E amplifier the inverse Class-E amplifier offers the potential for high efficiency at increased output power as well as higher peak output power levels than are available with a conventional Class-E amplifier. Further the inverse Class-E amplifier provides more flexibility for deployment with a pulsewidth modulator as the means of producing full-carrier amplitude modulation (AM) due to its ability to operate to high AM modulation indices.

Microsatellite analysis for determination of the mutagenicity of extremely low-frequency electromagnetic fields and ionising radiation in vitro.

Extremely low-frequency electromagnetic fields (ELF-EMF) have been reported to induce lesions in DNA and to enhance the mutagenicity of ionising radiation. However, the significance of these findings is uncertain because the determination of the carcinogenic potential of EMFs has largely been based on investigations of large chromosomal aberrations. Using a more sensitive method of detecting DNA damage involving microsatellite sequences, we observed that exposure of UVW human glioma cells to ELF-EMF alone at a field strength of 1 mT (50 Hz) for 12 h gave rise to 0.011 mutations/locus/cell. This was equivalent to a 3.75-fold increase in mutation induction compared with unexposed controls. Furthermore, ELF-EMF increased the mutagenic capacity of 0.3 and 3 Gy gamma-irradiation by factors of 2.6 and 2.75, respectively. These results suggest not only that ELF-EMF is mutagenic as a single agent but also that it can potentiate the mutagenicity of ionising radiation. Treatment with 0.3 Gy induced more than 10 times more mutations per unit dose than irradiation with 3 Gy, indicating hypermutability at low dose.

DNA and chromosomal damage in response to intermittent extremely low-frequency magnetic fields.

Considerable controversy still exists as to whether electric and magnetic fields (MF) at extremely low frequencies are genotoxic to humans. The aim of this study was to test the ability of alternating magnetic fields to induce DNA and chromosomal damage in primary human fibroblasts. Single- and double-strand breaks were quantified using the alkaline comet assay and the gammaH2AX-foci assay, respectively. Chromosomal damage was assayed for unstable aberrations, sister chromatid exchange and micronuclei. Cells were exposed to switching fields - 5min on, 10min off - for 15h over the range 50-1000microT. Exposure to ionizing radiation was used as a positive-effect calibration. In this study two separate MF exposure systems were used. One was based on a custom-built solenoid coil system and the other on a commercial system almost identical to that used in previous studies by the EU REFLEX programme. With neither system could DNA damage or chromosomal damage be detected as a result of exposure of fibroblasts to switching MF. The sensitive gammaH2AX assay could also not detect significant DNA damage in the MF-exposed fibroblasts, although the minimum threshold for this assay was equivalent to an X-ray dose of 0.025Gy. Therefore, with comparable MF parameters employed, this study could not confirm previous studies reporting significant effects for both the alkaline and neutral comet assays and chromosomal aberration induction.

Series-L/parallel-tuned comparison with shunt-C/series-tuned class-E power amplifier

An analysis of the operation of a series-L/parallel-tuned class-E amplifier and its equivalence to the classic shunt-C/series-tuned class-E amplifier are presented. The first reported closed form design equations for the series-L/parallel-tuned topology operating under ideal switching conditions are given. Furthermore, a design procedure is introduced that allows the effect that nonzero switch resistance has on amplifier performance efficiency to be accounted for. The technique developed allows optimal circuit components to be found for a given device series resistance. For a relatively high value of switching device ON series resistance of 4O, drain efficiency of around 66% for the series-L/parallel-tuned topology, and 73% for the shunt-C/series-tuned topology appear to be the theoretical limits. At lower switching device series resistance levels, the efficiency performance of each type are similar, but the series-L/parallel-tuned topology offers some advantages in terms of its potential for MMIC realisation. Theoretical analysis is confirmed by numerical simulation for a 500mW (27dBm), 10% bandwidth, 5 V series-L/parallel-tuned, then, shunt-C/series-tuned class E power amplifier, operating at 2.5 GHz, and excellent agreement between theory and simulation results is achieved. The theoretical work presented in the paper should facilitate the design of high-efficiency switched amplifiers at frequencies commensurate with the needs of modern mobile wireless applications in the microwave frequency range, where intrinsically low-output-capacitance MMIC switching devices such as pHEMTs are to be used.

The challenge of revealing and tailoring the dynamics of radio-frequency plasmas

The complex dynamics of ionization and excitation mechanisms in capacitively coupled radio-frequency plasmas is discussed for single- and dual-frequency operations in low-pressure and atmospheric pressure plasmas. Electrons are energized through the dynamics of electric fields in the vicinity of the plasma boundary sheaths. Distinctly different power dissipation mechanisms can either co-exist or initiate mode transitions exhibiting characteristic spatio-temporal ionization structures. Phase resolved optical emission spectroscopy, in combination with adequate modelling of the population dynamics of excited states, and numerical simulations reveal dissipation associated with sheath expansion, sheath collapse, transient electron avalanches and wave–particle interactions. In dual-frequency systems the relative phase between the two frequency components provides additional strategies to tailor the plasma dynamics.

The influence of the relative phase between the driving voltages on electron heating in asymmetric dual frequency capacitive discharges

The influence of the relative phase between the driving voltages on electron heating in asymmetric phase-locked dual frequency capacitively coupled radio frequency plasmas operated at 2 and 14 MHz is investigated. The basis of the analysis is a nonlinear global model with the option to implement a relative phase between the two driving voltages. In recent publications it has been reported that nonlinear electron resonance heating can drastically enhance the power dissipation to electrons at moments of sheath collapse due to the self-excitation of nonlinear plasma series resonance (PSR) oscillations of the radio frequency current. This work shows that depending on the relative phase of the driving voltages, the total number and exact moments of sheath collapse can be influenced. In the case of two consecutive sheath collapses a substantial increase in dissipated power compared with the known increase due to a single PSR excitation event per period is observed. Phase resolved optical emission spectroscopy (PROES) provides access to the excitation dynamics in front of the driven electrode. Via PROES the propagation of beam-like energetic electrons immediately after the sheath collapse is observed. In this work we demonstrate that there is a close relation between moments of sheath collapse, and thus excitation of the PSR, and beam-like electron propagation. A comparison of simulation results to experiments in a single and dual frequency discharge shows good agreement. In particular the observed influence of the relative phase on the dynamics of a dual frequency discharge is described by means of the presented model. Additionally, the analysis demonstrates that the observed gain in dissipation is not accompanied by an increase in the electrode’s dc-bias voltage which directly addresses the issue of separate control of ion flux and ion energy in dual frequency capacitively coupled radio frequency plasmas.

Perturbed frequency-selective surfaces fabricated on large thin polymer membranes for multiband infrared applications

The design, fabrication, and characterization of single-screen perturbed frequency-selective surfaces (FSS) at infrared frequencies for single and multiband applications are reported. Single-band FSS based on parallel strips have been perturbed by decreasing the length of every second strip within the array in order to achieve dual band-stop responses. The same principle has been extended to design FSS exhibiting tri- and quadreflection bands. In addition, strip FSSs have been perturbed by replacing every second strip for a metallic ring, resulting in dual-band filters with different polarization responses of the bands. These designs have been fabricated on large thin polyimide membranes using sacrificial silicon wafers. An oxide interlayer between the sacrificial silicon wafer and the polyimide membrane is employed to stop the silicon etching and is wet etched subsequently by a solution of ammonium fluoride and acetic acid that does not attack either the polyimide membrane or the aluminium FSS elements. Fourier transform infrared spectroscopy measurements are presented to validate the predicted responses of the fabricated prototypes.

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.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa. Heredity (2010) 104, 148-154; doi:10.1038/hdy.2009.84; published online 29 July 2009