Molecular dissection of the human antibody response to the structural repeat epitope of Plasmodium falciparum sporozoite from a protected donor

BACKGROUND: The circumsporozoite surface protein is the primary target of human antibodies against Plasmodium falciparum sporozoites, these antibodies are predominantly directed to the major repetitive epitope (Asn-Pro-Asn-Ala)(n), (NPNA)(n). In individuals immunized by the bites of irradiated Anopheles mosquitoes carrying P. falciparum sporozoites in their salivary glands, the anti-repeat response dominates and is thought by many to play a role in protective immunity. METHODS: The antibody repertoire from a protected individual immunized by the bites of irradiated P. falciparum infected Anopheles stephensi was recapitulated in a phage display library. Following affinity based selection against (NPNA)(3 )antibody fragments that recognized the PfCSP repeat epitope were rescued. RESULTS: Analysis of selected antibody fragments implied the response was restricted to a single antibody fragment consisting of V(H)3 and V(κ)I families for heavy and light chain respectively with moderate affinity for the ligand. CONCLUSION: The dissection of the protective antibody response against the repeat epitope revealed that the response was apparently restricted to a single V(H)/V(L )pairing (PfNPNA-1). The affinity for the ligand was in the μM range. If anti-repeat antibodies are involved in the protective immunity elicited by exposure to radiation attenuated P. falciparum sporozoites, then high circulating levels of antibodies against the repeat region may be more important than intrinsic high affinity for protection. The ability to attain and sustain high levels of anti-(NPNA)(n )will be one of the key determinants of efficacy for a vaccine that relies upon anti-PfCSP repeat antibodies as the primary mechanism of protective immunity against P. falciparum

The impact of deep-sea fisheries and implementation of the UNGA Resolutions 61/105 and 64/72. Report of an international scientific workshop

The scientific workshop to review fisheries management, held in Lisbon in May 2011, brought together 22 scientists and fisheries experts from around the world to consider the United Nations General Assembly (UNGA) resolutions on high seas bottom fisheries: what progress has been made and what the outstanding issues are. This report summarises the workshop conclusions, identifying examples of good practice and making recommendations in areas where it was agreed that the current management measures fall short of their target

Specific Heat of Liquid Helium in Zero Gravity very near the Lambda Point

We report the details and revised analysis of an experiment to measure the specific heat of helium with subnanokelvin temperature resolution near the lambda point. The measurements were made at the vapor pressure spanning the region from 22 mK below the superfluid transition to 4 uK above. The experiment was performed in earth orbit to reduce the rounding of the transition caused by gravitationally induced pressure gradients on earth. Specific heat measurements were made deep in the asymptotic region to within 2 nK of the transition. No evidence of rounding was found to this resolution. The optimum value of the critical exponent describing the specific heat singularity was found to be a = -0.0127+ - 0.0003. This is bracketed by two recent estimates based on renormalization group techniques, but is slightly outside the range of the error of the most recent result. The ratio of the coefficients of the leading order singularity on the two sides of the transition is A+/A- =1.053+ - 0.002, which agrees well with a recent estimate. By combining the specific heat and superfluid density exponents a test of the Josephson scaling relation can be made. Excellent agreement is found based on high precision measurements of the superfluid density made elsewhere. These results represent the most precise tests of theoretical predictions for critical phenomena to date.Comment: 27 Pages, 20 Figure

Developing focal construct technology for in vivo diagnosis of osteoporosis

Osteoporosis is a prevalent bone disease around the world, characterised by low bone mineral density and increased fracture risk. Currently, the gold standard for identifying osteoporosis and increased fracture risk is through quantification of bone mineral density (BMD), using dual energy X-ray absorption (DEXA). However, the use of BMD to diagnose osteoporosis is not without limitation and arguably the risk of osteoporotic fracture should be determined collectively by bone mass, architecture and physicochemistry of the mineral composite building blocks. Rather than depending exclusively on the 'mass' of bone, our previous research investigated predicting the risk of fracture using 'bone quality'. The work highlighted that the material properties of OP tissue differ significantly to that of 'normal' bone and for the first time reported the clinical value of new biomarkers (obtained from X-ray scatter signatures) for fracture risk prediction. Thus, in order to improve fracture prediction models, diagnostic tools need to be developed which not only measure bone mineral density, but also bone quality. This pilot study builds on our previous work and aims to develop a new technology, Focal Construct Technology (FCT), which is hoped can measure XRD signatures in vivo. Our previous work was performed entirely with interrogating probes applied in transmission mode. This has some disadvantages that would be overcome were reflection mode employed. This study involves the creation of unique, high impact data with the potential to form the basis of a new generation of medical diagnostic instrumentation. A systematic series of conventional reflection mode ex vivo experiments were performed in which bone specimens were examined through increasing thicknesses of overlaying muscle/fat/skin. Further, we applied FCT to these geometries. This had not previously been attempted and required some initial modelling to ensure correct topologies of the hollow beams. The results from this study suggest it may be possible to obtain the parameters in vivo with the same precision as those obtained within the laboratory when using FCT

Climatological Statistics of Extreme Geomagnetic Fluctuations With Periods From 1 s to 60 min

Using a global database of 125 magnetometers covering several decades, we present occurrence statistics for fluctuations of the horizontal geomagnetic field (dBh/dt) exceeding the 99.97th percentile (P99.97) for both ramp changes (Rn) and the root-mean-square (Sn) of fluctuations over periods, τ, from 1 to 60 min and describe their variation with geomagnetic latitude and magnetic local time (MLT). Rates of exceedance are explained by reference to the magneto-ionospheric processes dominant in different latitude and MLT sectors, including ULF waves, interplanetary shocks, auroral substorm currents, and traveling convection vortices. By fitting generalized Pareto tail distributions above P99.97, we predict return levels (RLs) for Rn and Sn over return periods of between 5 and 500 years. P99.97 and RLs increase monotonically with frequency (1/τ) (with a few exceptions at auroral latitudes) and this is well modeled by quadratic functions whose coefficients vary smoothly with latitude. For UK magnetometers providing 1-s cadence measurements, the analysis is extended to cover periods from 1 to 60 s and empirical Magnetotelluric Transfer functions are used to predict percentiles and return levels of the geoelectric field over a wide frequency range (2 × 10−4 to 4 × 10−2 Hz) assuming a sinusoidal field fluctuation. These results help identify the principal causes of field fluctuations leading to extreme geomagnetically induced currents (GIC) in ground infrastructure over a range of timescales and they inform the choice of frequency dependence to use with dBh/dt as a GIC proxy

Application of coded apertures in tomographic head scanning

A circular ring tomograph, designated SPRINT, is under development for single photon emission tomography of the human head. Most data to date have been gathered using a single rotating slit inside the detector ring to define ray directions. As an alternative method, we have also investigated the use of multiplexed slit patterns consisting of a pseudorandom binary code. From theoretical considerations, one would expect that the substitution of the code for the single slit would have potential advantages in reducing statistical noise in tomographic images of small objects. It has been our experience that this improvement is marginal at best for the types of source distributions encountered in clinical brain imaging. However, the code shows substantial advantage in suppressing uncorrelated backgrounds and the effects of highly penetrating gamma ray components in the source.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24867/1/0000294.pd

Tissue chemistry and carbon allocation in seedlings of Pinus palustris subjected to elevated atmospheric CO2 and water stress

Longleaf pine (Pinus palustris Mill.) seedlings were grown in 45-1 pots and exposed to ambient or elevated (365 or 730 uamol CO2 mol-1 ) CO2 concentration in open-top chambers for 20 months. Two water-stress treatments (target values of -0.5 or -1.5 MPa xylem pressure potential) were imposed 19 weeks after initiation of the study. At harvest, tissues (needles, stems, taproots, coarse roots, and fine roots) were analyzed for carbon (C), nitrogen (N), nonpolar extractives (fats, waxes, and oils), nonstructural carbohydrates (sugars and starch), structural components (cellulose and lignin), and tannins. The greatest dry weights and lowest N concentrations occurred in tissues of plants grown at elevated CO 2 or with adequate water. Although allocation of C fractions among tissues was generally unaffected by treatments, concentrations of the analyzed compounds were influenced by treatments in needles and taproots, but not in stems and lateral roots. Needles and taproots of plants exposed to elevated CO2 had increased concentrations of nonstructural carbohydrates. Among plant tissues, elevated CO2 caused reductions in structural C concentrations and foliar concentrations of fats, waxes and oils

Experimental and theoretical studies of transport through large scale, partially aligned arrays of single-walled carbon nanotubes in thin film type transistors

Gate-modulated transport through partially aligned films of single-walled carbon nanotubes (SWNTs) in thin film type transistor structures are studied experimentally and theoretically. Measurements are reported on SWNTs grown by chemical vapor deposition with systematically varying degrees of alignment and coverage in transistors with a range of channel lengths and orientations perpendicular and parallel to the direction of alignment. A first principles stick-percolation-based transport model provides a simple, yet quantitative framework to interpret the sometimes counterintuitive transport parameters measured in these devices. The results highlight, for example, the dramatic influence of small degrees of SWNT misalignment on transistor performance and imply that coverage and alignment are correlated phenomena and therefore should be simultaneously optimized. The transport characteristics reflect heterogeneity in the underlying anisotropic metal-semiconductor stick-percolating network and cannot be reproduced by classical transport models. © 2007 American Chemical Society

Ionization degree of the electron-hole plasma in semiconductor quantum wells

The degree of ionization of a nondegenerate two-dimensional electron-hole plasma is calculated using the modified law of mass action, which takes into account all bound and unbound states in a screened Coulomb potential. Application of the variable phase method to this potential allows us to treat scattering and bound states on the same footing. Inclusion of the scattering states leads to a strong deviation from the standard law of mass action. A qualitative difference between mid- and wide-gap semiconductors is demonstrated. For wide-gap semiconductors at room temperature, when the bare exciton binding energy is of the order of T, the equilibrium consists of an almost equal mixture of correlated electron-hole pairs and uncorrelated free carriers.Comment: 22 pages, 6 figure