The Interaction of Anti-DNA Antibodies with DNA: Evidence for Unconventional Binding Mechanisms

Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus, a prototypic autoimmune disease. These antibodies bind to conserved sites on single-stranded and double-stranded DNA and display variable region somatic mutations consistent with antigen selection. Nevertheless, the interaction of anti-DNA with DNA has unconventional features. Anti-DNA antibodies bind by a mechanism called monogamous bivalency, in which stable interaction requires contact of both Fab sites with determinants on the same extended DNA molecule; the size of this DNA can be hundreds to thousands of bases, especially in solid phase assays. This binding also requires the presence of the Fc portion of IgG, a binding mechanism known as Fc-dependent monogamous bivalency. As shown by the effects of ionic strength in association and dissociation assays, anti-DNA binding is primarily electrostatic. Like anti-DNA autoantibodies, anti-DNA antibodies that bind specifically to non-conserved sites on bacterial DNA, a type of anti-DNA found in otherwise healthy individuals, also interact by monogamous bivalency. The unconventional features of anti-DNA antibodies may reflect the highly charged and polymeric nature of DNA and the need for molecular rearrangements to facilitate monogamous bivalency; the Fc portion contributes to binding in an as yet unknown way.     

Mathieu functions and their applications to scattering by a coatedstrip

The elliptic-cylinder harmonics, known as Mathieu (1868) functions, are reviewed. These functions are then used to describe EM scattering by confocal elliptic cylinders where each cylinder's dielectric constant is different. A peculiarity of this problem is that the Mathieu functions in different regions are not orthogonal at regional boundaries. Hence, each boundary couples all harmonics from both sides together, and infinite sets of coefficients must be simultaneously evaluated. Numerical results are given for the special case where the innermost region is a perfect conductor. The authors consider both TE and TM illumination. Only normal incidence is actually treated, although oblique generalization is conceptually easy     

Ion implantation doping of OMCVD grown GaN

Doping by ion implantation using Si, O, Mg, and Ca has been studied in single crystal semi-insulating and n-type GaN grown on a-sapphire substrates. The n-and p-type dopants used in this study are Si and O; Mg and Ca, respectively. Room temperature activation of Si and O donors has been achieved after 1150°C annealing for 120 s. The activation of Mg and Ca acceptors is too low to measure at both room temperature and 300°C. Using higher doses to achieve a measurable p-type conduction increases the amount of damage created by the implantation. Rutherford back scattering measurements on this material indicate that the damage is still present even after the maximum possible heat treatment. Secondary ion mass spectrometry measurements have indicated a redistribution in the measured profiles of Mg due to annealing.     

Characteristics of planar n-p junction diodes made bydouble-implantations into 4H-SiC

Double implantation technology consisting of deep-range acceptor followed by shallow-range donor implantation was used to fabricate planar n⁺-p junction diodes in 4H-SiC. Either Al or B was used as the acceptor species and N as the donor species with all implants performed at 700°C and annealed at 1650°C with an AlN encapsulant. The diodes were characterized for their current-voltage (I-V) and capacitance-voltage (C-V) behavior over the temperature range 25°C-400°C, and reverse recovery transient behavior over the temperature range 25°C-200°C. At room temperature, the B-implanted diodes exhibited a reverse leakage current of 5×10^-8 A/cm² at a reverse bias of -20 V and a carrier lifetime of 7.4 ns     

A mesoscopic ballistic electron mixer with efficient frequencyconversion at radio frequency

The voltage-current characteristic of a four-terminal mesoscopic cross is grossly nonlinear, exhibiting two clear regions of negative differential resistance (NDR). This behavior is potentially useful in millimeter wave detectors since these small devices have very low parasitic capacitance and great sensitivity. The device exploits a planar GaAs technology which lends itself to integrated systems. We have exploited one of the NDR regions (at a current of only 1.9 μA) to carry out frequency conversion. At low frequency we observed efficient frequency doubling, with the second harmonic exceeding the fundamental by up to 10 dB at the output. We have also operated the device at radio frequency (5 MHz) and demonstrated both asynchronous and heterodyne amplitude demodulation. The effect of DC current bias was examined and it was shown that biasing the device close to the NDR gave the optimum frequency conversion. A conversion loss in the heterodyne mixer circuit of 3 dB was achieved     

100 mK bolometers for the submillimetre common-user bolometer array (scuba) I. Design and construction

We describe the design and construction of bolometric detectors for SCUBA - the Submillimetre Common-User Bolometer Array for the James Clerk Maxwell Telescope in Hawaii. The instrument contains 131 individual detectors, in two arrays, optimized for the submillimetre atmospheric transmission windows. The detectors are cooled by dilution refrigeration to a temperature of 100 mK, so that the receiver performance will be limited by photon noise from the sky and telescope background in all wavebands. A future paper will describe the performance of the detectors with reference to typical data obtained during the laboratory commissioning period.     

The effect of size of sub-sample on mineral analysis values of apple fruits

Apple fruits were divided into opposite sectors of different sizes, and the mineral analyses of the sectors were compared with whole fruit values. Opposite sectors as small 8-12% of whole fruit weight were found to be as representative as larger sectors. There was no evidence of either a constant or a proportional bias arising as a result of sub-sampling. Sub-sampling variation was greater for Ca than for N, P, K and Mg.     

Accelerating Machine-Learning Algorithms on FPGAs using Pattern-Based Decomposition

Machine-learning algorithms are employed in a wide variety of applications to extract useful information from data sets, and many are known to suffer from super-linear increases in computational time with increasing data size and number of signals being processed (data dimension). Certain principal machine-learning algorithms are commonly found embedded in larger detection, estimation, or classification operations. Three such principal algorithms are the Parzen window-based, non-parametric estimation of Probability Density Functions (PDFs), K-means clustering and correlation. Because they form an integral part of numerous machine-learning applications, fast and efficient execution of these algorithms is extremely desirable. FPGA-based reconfigurable computing (RC) has been successfully used to accelerate computationally intensive problems in a wide variety of scientific domains to achieve speedup over traditional software implementations. However, this potential benefit is quite often not fully realized because creating efficient FPGA designs is generally carried out in a laborious, case-specific manner requiring a great amount of redundant time and effort. In this paper, an approach using pattern-based decomposition for algorithm acceleration on FPGAs is proposed that offers significant increases in productivity via design reusability. Using this approach, we design, analyze, and implement a multi-dimensional PDF estimation algorithm using Gaussian kernels on FPGAs. First, the algorithm’s amenability to a hardware paradigm and expected speedups are predicted. After implementation, actual speedup and performance metrics are compared to the predictions, showing speedup on the order of 20× over a 3.2 GHz processor. Multi-core architectures are developed to further improve performance by scaling the design. Portability of the hardware design across multiple FPGA platforms is also analyzed. After implementing the PDF algorithm, the value of pattern-based decomposition to support reuse is demonstrated by rapid development of the K-means and correlation algorithms.     

EM pickup and scattering by a wire

This article treats pickup and scattering by a single wire in free space or over a ground plane. The wire may be uniform or nonuniform and infinite or finite. We only treat the case where wire radius is so small compared to a wavelength and the other problem dimensions that scattering by the wire is independent of azimuth. Solutions based directly on Maxwell's equations are compared with solutions based on the telegrapher's equations; for 1 mm radius Cu wire at 1 GHz, equilibrium CW currents as computed from the two models, for a uniform, infinite wire, differ by 6 dB. In general, the wire-current solutions are separated into a homogeneous part and a particular or driven part. The driven part couples and scatters fields, while,at least on an infinite wire in the far field, the homogeneous part does not     

Characteristics of the heterologously expressed human lanosterol 14α‐demethylase (other names: P45014DM,CYP51, P45051) and inhibition of the purified human and Candida albicans CYP51 with azole antifungal agents

Human and Candida albicans CYP51 were purified to homogeneity after GAL10‐based heterologous expression in yeast in order to resolve the basis for the selective inhibition of the fungal enzyme over the human orthologue by the azole drugs ketoconazole and itraconazole, used in the treatment of systemic fungal infection. The purified proteins have similar spectral characteristics, both giving a maximum at 448 nm in reduced carbon monoxide difference spectra. Substrate affinity constants of 20·8 and 29·4 μM and V_max of 0·15 and 0·47 nmol/min/nmol were observed for C. albicans and human enzymes, respectively, in reconstituted enzymatic assays, using an intermediate of the demethylation reaction [32‐³H]‐3β‐hydroxylanost‐7‐en‐32‐ol as the substrate. Both enzymes gave similar type II spectra on titration with drugs, but a reduced affinity was observed for human CYP51 using the ability of carbon monoxide to displace the drug as a ligand and by calculation of IC₅₀. However, although the results indicate higher affinity of the drugs for their target CYP51 in the major fungal pathogen C. albicans, when compared directly to CYP51 from humans, the difference was less than 10‐fold. This difference is an order of magnitude lower than previously reported data based on measurements using unpurified human CYP51 enzyme preparations. Consequently, increased azole doses to combat resistant candidaemia may well inhibit endogenous human CYP51 and the potential consequences are discussed. Copyright © 1999 John Wiley & Sons, Ltd.