Antibody deficiency due to a missense mutation in CD19 demonstrates the importance of the conserved tryptophan 41 in immunoglobulin superfamily domain formation.

Immunoglobulin superfamily (IgSF) domains are conserved structures present in many proteins in eukaryotes and prokaryotes. These domains are well-capable of facilitating sequence variation, which is most clearly illustrated by the variable regions in immunoglobulins (Igs) and T cell receptors (TRs). We studied an antibody-deficient patient suffering from recurrent respiratory infections and with impaired antibody responses to vaccinations. Patient's B cells showed impaired Ca(2+) influx upon stimulation with anti-IgM and lacked detectable CD19 membrane expression. CD19 sequence analysis revealed a homozygous missense mutation resulting in a tryptophan to cystein (W52C) amino acid change. The affected tryptophan is CONSERVED-TRP 41 located on the C-strand of the first extracellular IgSF domain of CD19 and was found to be highly conserved, not only in mammalian CD19 proteins, but in nearly all characterized IgSF domains. Furthermore, the tryptophan is present in all variable domains in Ig and TR and was not mutated in 117 Ig class-switched transcripts of B cells from controls, despite an overall 10% amino acid change frequency. In vitro complementation studies and CD19 western blotting of patient's B cells demonstrated that the mutated protein remained immaturely glycosylated. This first missense mutation resulting in a CD19 deficiency demonstrates the crucial role of a highly conserved tryptophan in proper folding or stability of IgSF domains.

Cross-correlation frequency resolved optical gating analysis of broadband continuum generation in photonic crystal fiber: Simulations and experiments

Numerical simulations are used to study the temporal and spectral characteristics of broadband supercontinua generated in photonic crystal fiber. In particular, the simulations are used to follow the evolution with propagation distance of the temporal intensity, the spectrum, and the cross-correlation frequency resolved optical gating (XFROG) trace. The simulations allow several important physical processes responsible for supercontinuum generation to be identified and, moreover, illustrate how the XFROG trace provides an intuitive means of interpreting correlated temporal and spectral features of the supercontinuum. Good qualitative agreement with preliminary XFROG measurements is observed. © 2002 Optical Society of America.

Vulnerability of coastal ecosystems to changes in harmful algal bloom distribution in response to climate change: projections based on model analysis

Harmful algal blooms (HABs), those proliferations of algae that can cause fish kills, contaminate seafood with toxins, form unsightly scums, or detrimentally alter ecosystem function have been increasing in frequency, magnitude, and duration worldwide. Here, using a global modeling approach, we show, for three regions of the globe, the potential effects of nutrient loading and climate change for two HAB genera, pelagic Prorocentrum and Karenia, each with differing physiological characteristics for growth. The projections (end of century, 2090-2100) are based on climate change resulting from the A1B scenario of the Intergovernmental Panel on Climate Change Institut Pierre Simon Laplace Climate Model (IPCC, IPSL-CM4), applied in a coupled oceanographic-biogeochemical model, combined with a suite of assumed physiological 'rules' for genera-specific bloom development. Based on these models, an expansion in area and/or number of months annually conducive to development of these HABs along the NW European Shelf-Baltic Sea system and NE Asia was projected for both HAB genera, but no expansion (Prorocentrum spp.), or actual contraction in area and months conducive for blooms (Karenia spp.), was projected in the SE Asian domain. The implications of these projections, especially for Northern Europe, are shifts in vulnerability of coastal systems to HAB events, increased regional HAB impacts to aquaculture, increased risks to human health and ecosystems, and economic consequences of these events due to losses to fisheries and ecosystem services.

Numerical analysis of bodyworn UHF antenna systems

Bodyworn antennas are found in a wide range of medical, military and personal communication applications, yet reliable communication from the surface of the human body still presents a range of engineering challenges. At UHF and microwave frequencies, bodyworn antennas can suffer from reduced efficiency due to electromagnetic absorption in tissue, radiation pattern fragmentation and variations in feed-point impedance. The significance and nature of these effects are system specific and depend on the operating frequency, propagation environment and physical constraints on the antenna itself. This paper describes how numerical electromagnetic modelling techniques such as FDTD (finite-difference time-domain) can be used in the design of bodyworn antennas. Examples are presented for 418 MHz, 916 .5 MHz and 2 . 45 GHz, in the context of both biomedical signalling and wireless personal-area networking applications such as the Bluetooth(TM)* wireless technology.

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.

A time-domain approach to the analysis and modeling of on-body propagation characteristics using synchronized measurements at 2.45 GHz

Modeling of on-body propagation channels is of paramount importance to those wishing to evaluate radio channel performance for wearable devices in body area networks (BANs). Difficulties in modeling arise due to the highly variable channel conditions related to changes in the user's state and local environment. This study characterizes these influences by using time-series analysis to examine and model signal characteristics for on-body radio channels in user stationary and mobile scenarios in four different locations: anechoic chamber, open office area, hallway, and outdoor environment. Autocorrelation and cross-correlation functions are reported and shown to be dependent on body state and surroundings. Autoregressive (AR) transfer functions are used to perform time-series analysis and develop models for fading in various on-body links. Due to the non-Gaussian nature of the logarithmically transformed observed signal envelope in the majority of mobile user states, a simple method for reproducing the failing based on lognormal and Nakagami statistics is proposed. The validity of the AR models is evaluated using hypothesis testing, which is based on the Ljung-Box statistic, and the estimated distributional parameters of the simulator output compared with those from experimental results.

Modeling Frequency-Dependent Boundaries as Digital Impedance Filters in FDTD and K-DWM Room Acoustics Simulations

A new method for modeling-frequency-dependent boundaries in finite-difference time-domain (FDTD) and Kirchhoff variable digital waveguide mesh (K-DWM) room acoustics simulations is presented. The proposed approach allows the direct incorporation of a digital impedance filter (DIF) in the Multidimensional (2D or 3D) FDTD boundary model of a locally reacting surface. An explicit boundary update equation is obtained by carefully constructing a Suitable recursive formulation. The method is analyzed in terms of pressure wave reflectance for different wall impedance filters and angles of incidence. Results obtained from numerical experiments confirm the high accuracy of the proposed digital impedance filter boundary model, the reflectance of which matches locally reacting surface (LRS) theory closely. Furthermore a numerical boundary analysis (NBA) formula is provided as a technique for an analytic evaluation of the numerical reflectance of the proposed digital impedance filter boundary formulation.

Variations in Apolipoprotein E Frequency With Age in a Pooled Analysis of a Large Group of Older People

Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms e2, e3, and e4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE e4 isoform with increasing age (?2 for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the e3 isoform (?2 for trend = 11.3 (1 df); P = 0.001). The association with age was strongest in e4 homozygotes; the frequency of e4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the e3/e4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevity.