Rapid cloning of high-affinity human monoclonal antibodies against influenza virus

Pre-existing neutralizing antibody provides the first line of defence against pathogens in general. For influenza virus, annual vaccinations are given to maintain protective levels of antibody against the currently circulating strains. Here we report that after booster vaccination there was a rapid and robust influenza-specific IgG+ antibody-secreting plasma cell (ASC) response that peaked at approximately day 7 and accounted for up to 6% of peripheral blood B cells. These ASCs could be distinguished from influenza-specific IgG+ memory B cells that peaked 14-21 days after vaccination and averaged 1% of all B cells. Importantly, as much as 80% of ASCs purified at the peak of the response were influenza specific. This ASC response was characterized by a highly restricted B-cell receptor (BCR) repertoire that in some donors was dominated by only a few B-cell clones. This pauci-clonal response, however, showed extensive intraclonal diversification from accumulated somatic mutations. We used the immunoglobulin variable regions isolated from sorted single ASCs to produce over 50 human monoclonal antibodies (mAbs) that bound to the three influenza vaccine strains with high affinity. This strategy demonstrates that we can generate multiple high-affinity mAbs from humans within a month after vaccination. The panel of influenza-virus-specific human mAbs allowed us to address the issue of original antigenic sin (OAS): the phenomenon where the induced antibody shows higher affinity to a previously encountered influenza virus strain compared with the virus strain present in the vaccine. However, we found that most of the influenza-virus-specific mAbs showed the highest affinity for the current vaccine strain. Thus, OAS does not seem to be a common occurrence in normal, healthy adults receiving influenza vaccination.     

Identity of Mertensia oblongifolia (Nutt.) G. Don (Boraginaceae) and its allies in western North America

The current status of Mertensia oblongifolia (Nutt.) G. Don and its allied taxa is surveyed. On the bases of continuously coherent morphological characters and/or regionally correlated variations, more than 30 taxa, including species, subspecies, varieties, and 1 forma, previously considered different from M. oblongifolia , are now placed under synonymy of this species. Those taxa currently known as M. fusiformis Greene, M. bakeri Greene, and M. bakeri var. osterhoutii Williams are among the new synonyms. Typification, taxonomy, and morphological problems of M. oblongifolia are discussed.     

Effect of controlled rolling on the martensitic hardenability of dual phase steel

The C-Mn and C-Mn-Nb steels were thermo-mechanically processed to develop dual phase steel and to study the effect of controlled rolling on the martensitic hardenability of austenite. The steel specimens were intercritically annealed at 790℃, rolled at that temperature to the reductions of 10%, 23%, and 47% and immediately cooled at different rates. Quantitative metallography was used to construct the microstructure map, which illustrated that increasing deformation progressively reduced the proportion of new ferrite formed at all cooling rates and increased the amount of martensite at fast and intermediate rates. The martensitic hardenability of austenite remaining after all the rolling reductions was plotted as a function of cooling rates. It was observed that for the austenite-martensite conversion efficiencies greater than about 25%, controlled rolling increased the martensitic hardenability of austenite.     

Effect of silica fume on the fresh and hardened properties of fly ash-based self-compacting geopolymer concrete

The effect of silica fume on the fresh and hardened properties of fly ash-based self-compacting geopolymer concrete (SCGC) was investigated in this paper. The work focused on the concrete mixes with a fixed water-to-geopolymer solid (W/Gs) ratio of 0.33 by mass and a constant total binder content of 400 kg/m3. The mass fractions of silica fume that replaced fly ash in this research were 0wt%, 5wt%, 10wt%, and 15wt%. The workability-related fresh properties of SCGC were assessed through slump flow, V-funnel, and L-box test methods. Hardened concrete tests were limited to compressive, splitting tensile and flexural strengths, all of which were measured at the age of 1, 7, and 28 d after 48-h oven curing. The results indicate that the addition of silica fume as a partial replacement of fly ash results in the loss of workability; nevertheless, the mechanical properties of hardened SCGC are significantly improved by incorporating silica fume, especially up to 10wt%. Applying this percentage of silica fume results in 4.3% reduction in the slump flow; however, it increases the compressive strength by 6.9%, tensile strength by 12.8% and flexural strength by 11.5%.     

Correlated binocular activity guides recovery from monocular deprivation

Monocular deprivation (MD) has much more rapid and severe effects on the ocular dominance of neurons in the primary visual cortex (V1) than does binocular deprivation. This finding underlies the widely held hypothesis that the developmental plasticity of ocular dominance reflects competitive interactions for synaptic space between inputs from the two eyes. According to this view, the relative levels of evoked activity in afferents representing the two eyes determine functional changes in response to altered visual experience. However, if the deprived eye of a monocularly deprived kitten is simply reopened, there is substantial physiological and behavioural recovery, leading to the suggestion that absolute activity levels, or some other non-competitive mechanisms, determine the degree of recovery from MD. Here we provide evidence that correlated binocular input is essential for such recovery. Recovery is far less complete if the two eyes are misaligned after a period of MD. This is a powerful demonstration of the importance of cooperative, associative mechanisms in the developing visual cortex.