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

Long-Time Asymptotics for Solutions of the NLS Equation with a Delta Potential and Even Initial Data

We consider the one-dimensional focusing nonlinear Schr\"odinger equation (NLS) with a delta potential and even initial data. The problem is equivalent to the solution of the initial/boundary problem for NLS on a half-line with Robin boundary conditions at the origin. We follow the method of Bikbaev and Tarasov which utilizes a B\"acklund transformation to extend the solution on the half-line to a solution of the NLS equation on the whole line. We study the asymptotic stability of the stationary 1-soliton solution of the equation under perturbation by applying the nonlinear steepest-descent method for Riemann-Hilbert problems introduced by Deift and Zhou. Our work strengthens, and extends, earlier work on the problem by Holmer and Zworski

On the dynamics of rational solutions for 1-D generalized Volterra system

The Hirota bilinear formalism and soliton solutions for a generalized Volterra system is presented. Also, starting from the soliton solutions, we obtain a class of nonsingular rational solutions using the "long wave" limit procedure of Ablowitz and Satsuma, and appropriate "gauge" transformations. Their properties are also discussed and it is shown that these solutions interact elastically with no phase shift.Comment: 9 pages, Late

A review of data on abundance, trends in abundance, habitat use and diet of ice-breeding seals in the Southern Ocean

The development of models of marine ecosystems in the Southern Ocean is becoming increasingly important as a means of understanding and managing impacts such as exploitation and climate change. Collating data from disparate sources, and understanding biases or uncertainties inherent in those data, are important first steps for improving ecosystem models. This review focuses on seals that breed in ice habitats of the Southern Ocean (i.e. crabeater seal, Lobodon carcinophaga; Ross seal, Ommatophoca rossii; leopard seal, Hydrurga leptonyx; and Weddell seal, Leptonychotes weddellii). Data on populations (abundance and trends in abundance), distribution and habitat use (movement, key habitat and environmental features) and foraging (diet) are summarised, and potential biases and uncertainties inherent in those data are identified and discussed. Spatial and temporal gaps in knowledge of the populations, habitats and diet of each species are also identified

Comparison of coal liquefaction processes. Final report on Task 006

Five processes were studied to determine which could give best results for supplying hydrocarbon fuels to replace petroleum products. The processes were Fischer-Tropsch; M-Gasoline; H-Coal; Exxon Donor Solvent; and Solvent Refined Coal. The conclusions of the study are that all of the processes are considered commercially feasible and, because the different products from the different processes will meet different market demands, any significant future liquids from coal market will probably use some of each of these processes. The anticipated conversion efficiency values are given to indicate resource utilization. Simplified capital costs are approximated for each process. These are used in combination with product amounts and relative values to achieve a cost ranking. Because the study was concerned solely with liquid products, Fischer-Tropsch was at a disadvantage. The remaining four were relatively close and a final decision would depend upon the actual end use requirements. For a situation with residual fuels selling at severe discounts, M-Gasoline and H-Coal (Syncrude Mode) were the better choices

Preserving the palaeoenvironmental record in Drylands: Bioturbation and its significance for luminescence-derived chronologies

Luminescence (OSL) dating has revolutionised the understanding of Late Pleistocene dryland activity. However, one of the key assumptions for this sort of palaeoenvironmental work is that sedimentary sequences have been preserved intact, enabling their use as proxy indicators of past changes. This relies on stabilisation or burial soon after deposition and a mechanism to prevent any subsequent re-mobilisation. As well as a dating technique OSL, especially at the single grain level, can be used to gain an insight into post-depositional processes that may distort or invalidate the palaeoenvironmental record of geological sediment sequences. This paper explores the possible impact of bioturbation (the movement of sediment by flora and fauna) on luminescence derived chronologies from Quaternary sedimentary deposits in Texas and Florida (USA) which have both independent radiocarbon chronologies and archaeological evidence. These sites clearly illustrate the ability of bioturbation to rejuvenate ancient weathered sandy bedrock and/or to alter depositional stratigraphies through the processes of exhumation and sub-surface mixing of sediment. The use of multiple OSL replicate measurements is advocated as a strategy for checking for bioturbated sediment. Where significant OSL heterogeneity is found, caution should be taken with the derived OSL ages and further measurements at the single grain level are recommended. Observations from the linear dunes of the Kalahari show them to have no bedding structure and to have OSL heterogeneity similar to that shown from the bioturbated Texan and Florida sites. The Kalahari linear dunes could have therefore undergone hitherto undetected post-depositional sediment disturbance which would have implications for the established OSL chronology for the region

Dispersion and collapse in stochastic velocity fields on a cylinder

The dynamics of fluid particles on cylindrical manifolds is investigated. The velocity field is obtained by generalizing the isotropic Kraichnan ensemble, and is therefore Gaussian and decorrelated in time. The degree of compressibility is such that when the radius of the cylinder tends to infinity the fluid particles separate in an explosive way. Nevertheless, when the radius is finite the transition probability of the two-particle separation converges to an invariant measure. This behavior is due to the large-scale compressibility generated by the compactification of one dimension of the space

Ku70 Serine 155 mediates Aurora B inhibition and activation of the DNA damage response

The Ku heterodimer (Ku70/Ku80) is the central DNA binding component of the classical non-homologous end joining (NHEJ) pathway that repairs DNA double-stranded breaks (DSBs), serving as the scaffold for the formation of the NHEJ complex. Here we show that Ku70 is phosphorylated on Serine 155 in response to DNA damage. Expression of Ku70 bearing a S155 phosphomimetic substitution (Ku70 S155D) in Ku70-deficient mouse embryonic fibroblasts (MEFs) triggered cell cycle arrest at multiple checkpoints and altered expression of several cell cycle regulators in absence of DNA damage. Cells expressing Ku70 S155D exhibited a constitutive DNA damage response, including ATM activation, H2AX phosphorylation and 53BP1 foci formation. Ku70 S155D was found to interact with Aurora B and to have an inhibitory effect on Aurora B kinase activity. Lastly, we demonstrate that Ku and Aurora B interact following ionizing radiation treatment and that Aurora B inhibition in response to DNA damage is dependent upon Ku70 S155 phosphorylation. This uncovers a new pathway where Ku may relay signaling to Aurora B to enforce cell cycle arrest in response to DNA damage

Recent Advances in Modeling Stellar Interiors

Advances in stellar interior modeling are being driven by new data from large-scale surveys and high-precision photometric and spectroscopic observations. Here we focus on single stars in normal evolutionary phases; we will not discuss the many advances in modeling star formation, interacting binaries, supernovae, or neutron stars. We review briefly: 1) updates to input physics of stellar models; 2) progress in two and three-dimensional evolution and hydrodynamic models; 3) insights from oscillation data used to infer stellar interior structure and validate model predictions (asteroseismology). We close by highlighting a few outstanding problems, e.g., the driving mechanisms for hybrid gamma Dor/delta Sct star pulsations, the cause of giant eruptions seen in luminous blue variables such as eta Car and P Cyg, and the solar abundance problem.Comment: Proceedings for invited talk at conference High Energy Density Laboratory Astrophysics 2010, Caltech, March 2010, submitted for special issue of Astrophysics and Space Science; 7 pages; 5 figure