Kinetics of somatic mutation in lymph node germinal centres

Somatic mutation activity in immunoglobulin V kappa genes during the response to the hapten 2-phenyl-5-oxazolone was measured in lymph node B-cell populations at various timepoints after footpad immunization. When the V kappa Ox1 genes rearranged to the J kappa 5 segment were amplified from genomic DNA using the polymerase chain reaction and sequenced, somatic mutations could be detected as early as day 4 after immunization. Somatic mutations were also detected after sequencing RNA from oxazolone-specific hybridomas derived from lymph node cells at day 4 after immunization. These early mutations were found mostly in cells with a germinal centre phenotype. No indication of selection at the population level by apoptosis was detected until day 7 after immunization. These results suggest somatic mutations can be induced very early during the immune response in lymph node cells, prior to the peak of clonal expansion and selection with regard to antigen binding.     

Numerical simulation of atmospheric boundary layer flow over isolated and vegetated hills using RAMS

Atmospheric boundary layer flows over hills are important in the analysis of wind energy systems, dispersion of pollutants in the atmosphere and many meteorological and engineering applications. The objective of this work is to use the Regional Atmospheric Modeling System (RAMS), a numerical mesoscale model generally used for weather forecast and atmospheric case studies, to simulate the flow over isolated hills, covered with vegetation of uniform and non-uniform roughness length. The ability of the model to simulate this type of flows is tested by comparison with actual microscale data. The flow is assumed to be two-dimensional and quasi-steady, and the atmosphere is dry under statically neutral and non-neutral stability conditions. The numerical grid covers a large physical domain, with constant mesh spacing in the horizontal direction and a telescopic mesh in the vertical direction. All cases studied show that the domain size, the boundary conditions and the turbulence models play an important role in the simulations. The numerical results indicate that the Mellor and Yamada turbulence model performs better than the Smagorinsky model. When compared to the Askervein, Black Mountain, Cooper's Ridge field data and other numerical and analytical results from the literature, the RAMS results predict reasonably well the vertical profiles of the mean velocity and of the absolute and relative speedups.     

Analysis of somatic mutation activity in multiple V kappa genes involved in the response to 2-phenyl-5-oxazolone

We have studied somatic mutation activity early in a response to 2-phenyl-5-oxazolone coupled to ovalbumin (phOx-OVA). Although the V kappa Ox1 gene rearranged to J kappa 5 is known to predominate in this response, other closely related V kappa genes are involved. We compared the introduction of point mutations into V kappa Ox1 genes and into a set of related V kappa genes rearranged to the same J kappa segment at two time points after primary immunization. The result showed that quantitation of mutations in a single rearrangement substrate leads to an underestimation of the total mutational activity. There is pronounced somatic mutation activity early within genes that may be absent later in the response. We also show that multiple somatic mutations can be detected in B cells from draining lymph nodes after foot-pad injection with phOx-OVA already at day 7 after immunization. The data suggest a system in which mutation acts early in the response on a wide range of substrates and that selection and expansion of high affinity paratopes occurs later.     

Mice with an inactivated joining chain locus have perturbed IgM secretion

A mouse with an inactivated joining chain locus was produced by gene targeting in embryonic stem cells by deleting the first exon. Heterozygote (J+/-) and homozygote (J-/-) offspring from these mice showed normal total serum immunoglobulin levels and a normal peripheral B cell compartment when compared to wild-type littermates. The distribution of serum immunoglobulin isotypes in serum was different; IgA levels were elevated while IgM levels were reduced in J-/- mice as compared to wild-type mice. High molecular weight serum IgM was reduced in J+/- and J-/- mice and instead found in oligomeric form of undefined structure. Furthermore, serum IgM from J+/- and J-/- mice showed a reduced ability to activate complement. The number of splenic and bone marrow IgM plaque-forming cells were reduced in unimmunized J+/- as well as in J-/- mice. Furthermore, the number of plaque-forming cells was reduced in B cells from both J+/- and J-/- mice after stimulation with lipopolysaccharide in vitro. The perturbation of IgM production in J-/- mice appears to affect a late stage of differentiation, because cells with intracellular IgM were readily detected both in vivo and in vitro. Finally, after immunization with T-dependent or T-independent antigens the IgM component of the immune response was reduced in J-/- mice while only a marginal reduction of the IgG response was detected.     

Antioxidant intake,plasma antioxidants and oxidative stress in a randomized,controlled, parallel,Mediterranean dietary intervention study on patients with rheumatoid arthritis

Background  

Previously we have reported that patients with rheumatoid arthritis (RA) obtained a significant reduction in disease activity by adopting a Mediterranean-type diet. The present study was carried out to investigate the antioxidant intake, the plasma levels of antioxidants and a marker of oxidative stress (malondialdehyde) during the study presented earlier.     

The performance of incremental redundancy schemes based on convolutional codes in the block-fading Gaussian collision channel

The throughput performance of incremental redundancy (INR) schemes, based on short constraint length convolutional codes, is evaluated for the block-fading Gaussian collision channel. Results based on simulations and union bound computations are compared to estimates of the achievable throughput performance with random binary and Gaussian coding in the limit of large block lengths, obtained through information outage considerations. For low channel loads, it is observed that INR schemes with binary convolutional codes and limited block length may provide throughput close to the achievable performance for binary random coding. However, for these low loads, compared to binary random coding, Gaussian random coding may provide significantly better throughput performance, which prompts the use of larger modulation constellations. For high channel loads, a relatively large gap in throughput performance between binary convolutional codes and binary random codes indicates a potential for extensive performance improvement by alternative coding strategies. Only small improvements of the throughput have been observed by increasing the complexity through increased state convolutional coding.     

On list sequence turbo decoding

An algorithm for decoding Turbo codes that combines conventional Turbo decoding and list sequence maximum a posteriori probability decoding is presented and evaluated. Compared to previous results on this theme, performance improvements in the order of 0.7 dB are obtained for Turbo codes with 514-b pseudorandom interleaving at a frame error rate of 10/sup -4/ on the additive white Gaussian noise channel.     

The max-log list algorithm (MLLA)-a list-sequence decoding algorithm that provides soft-symbol output

We present a soft decoding algorithm for convolutional codes that simultaneously yields soft-sequence output, i.e., list sequence (LS) decoding, and soft-symbol output. The max-log list algorithm (MLLA) introduced in this paper provides near-optimum soft-symbol output equal to that of the max-log maximum a posteriori (MAP) probability algorithm. Simultaneously, the algorithm produces an ordered list containing LS-MAP estimates. The MLLA exists in an optimum and a suboptimum version that are different in that the optimum version produces optimum LS-MAP decoding for arbitrary list lengths, while the suboptimum low-complexity version only provides the MAP, the second-order MAP, and the third-order MAP sequence estimates. For lists with more than three elements, MAP decoding is not guaranteed, but the LS decoding is close to the optimal. It is demonstrated that the suboptimum/optimum MLLA can be used to obtain the combination of soft-symbol and soft-sequence outputs at lower complexity than a previously published algorithm. Furthermore, the suboptimum MLLA is well suited for operation in an iterative list (turbo) decoder, since it is obtained by only minor modifications of the well-known Max-Log-MAP algorithm frequently used for decoding of the component codes of turbo codes. Another potential area of application for the suboptimum/optimum MLLA is joint source-channel LS decoding. Estimates of complexity and memory use, as well as performance evaluations of the suboptimum/optimum MLLA, are provided in this paper.     

Isocyanates and hydrogen cyanide in fumes from heated proteins and protein‐rich foods

Toxic compounds in cooking fumes could cause respiratory problems. In the present study, the formation of isocyanic acid (ICA), methyl isocyanate (MIC), and hydrogen cyanide (HCN) was studied during the heating of proteins or frying of protein‐rich foods. Heating was performed in an experimental setup using a tube oven set at 200‐500°C and in a kitchen when foods with different protein content were fried at a temperature around 300°C. ICA, MIC, and HCN were all generated when protein or meat was heated. Individual amino acids were also heated, and there was a significant positive correlation between their respective nitrogen content and the formation of the measured compounds. Gas from heated protein or meat also caused carbamylation in albumin. ICA, MIC, and HCN were also present in fumes generated when meat, egg, and halloumi were fried in a kitchen pan. The levels of ICA were here twice that of the Swedish occupational exposure limit. If ICA, MIC, and HCN in fumes from heated protein‐rich foods could contribute to the risk of airway dysfunction among those exposed is not clear, but it is important to avoid inhaling frying and grilling fumes and to equip kitchens with good exhaust ventilation.