Recent advances in malaria genomics and epigenomics

Malaria continues to impose a significant disease burden on low- and middle-income countries in the tropics. However, revolutionary progress over the last 3 years in nucleic acid sequencing, reverse genetics, and post-genome analyses has generated step changes in our understanding of malaria parasite (Plasmodium spp.) biology and its interactions with its host and vector. Driven by the availability of vast amounts of genome sequence data from Plasmodium species strains, relevant human populations of different ethnicities, and mosquito vectors, researchers can consider any biological component of the malarial process in isolation or in the interactive setting that is infection. In particular, considerable progress has been made in the area of population genomics, with Plasmodium falciparum serving as a highly relevant model. Such studies have demonstrated that genome evolution under strong selective pressure can be detected. These data, combined with reverse genetics, have enabled the identification of the region of the P. falciparum genome that is under selective pressure and the confirmation of the functionality of the mutations in the kelch13 gene that accompany resistance to the major frontline antimalarial, artemisinin. Furthermore, the central role of epigenetic regulation of gene expression and antigenic variation and developmental fate in P. falciparum is becoming ever clearer. This review summarizes recent exciting discoveries that genome technologies have enabled in malaria research and highlights some of their applications to healthcare. The knowledge gained will help to develop surveillance approaches for the emergence or spread of drug resistance and to identify new targets for the development of antimalarial drugs and perhaps vaccines

Volatility Surface and Skewness in Live Cattle Futures Price Distributions with Application to North American BSE Announcements

options markets, live cattle, volatility, pricing density function, Financial Economics, Livestock Production/Industries, Risk and Uncertainty,

Immunology of BCG vaccination in mice : implications for tuberculosis vaccination and for the use of BCG as a recombinant vaccine vector

The effect of vaccination dose on the immune response of mice to Mycobacterium bovis Bacille Calmette-Guerin (BCG) was examined. To assess T helper cell-type 1 (Th1) and -type 2 (Th2) responses, a very sensitive ELISPOT assay was developed. Using this assay, the numbers of BCG-specific interferon ɣ- and interleukin 4-producing spleen cells were used as indicators of the Th1 and Th2 responses, respectively. IgG1 and IgG2a serum antibody titers were also assessed. Mice were immunized with different doses of BCG, and their immune response to BCG antigen was determined at various times after vaccination. Low dose immunized mice developed predominantly Th1 responses and little antibody, while those given higher numbers of bacilli generated a mixed Th1/Th2 response and had significant antibody titers. Furthermore, mice given the lower doses of BCG developed an immune imprint that enabled them to resist development of a Th2 response on subsequent challenge with a higher dose of BCG, which generates a Th2 response in previously unexposed mice. The immune response of mice immunized with recombinant BCG (rBCG) expressing 'Escherichia coli' β-galactosidase was also characterized. Th1 cells predominated in the immune response to BCG antigen as well as to the expressed β-galactosidase antigen in low dose vaccinated mice. Moreover, the Th1 response to both antigens was stable after high dose challenge of low dose vaccinated animals indicating that immune imprinting had been established both to BCG and to the recombinant β-galactosidase antigen. The results indicate that the immune state that develops in mice upon vaccination with BCG depends on the initial dose of antigen administered, with low amounts of antigen leading to Th1 immunity, and relatively high amounts of antigen leading to Th2 immune responses. 'Mycobacterium tuberculosis ' is only controlled effectively by a cell-mediated immune response. Immunization with a relatively low dose of BCG, rather than the current standard dose, may provide greater immune protection against 'M. tuberculosis'. Moreover, low dose vaccination with rBCG expressing proteins of leishmania or HIV promises to be an effective means of vaccination against diseases caused by these pathogens, which can only be contained by a Th1 response

A high-resolution scalable meshless method for coupled steady poroelastic analysis, based on collocation with radial basis functions

This work describes the application of a novel meshless numerical technique, based on local collocation with radial basis functions (RBFs), to the solution of steady poroelastic problems. Its formulation allows scalability to large problem sizes, in contrast to traditional full-domain RBF collocation methods which are restricted to small datasets due to issues with numerical conditioning and computational cost. The proposed method is validated using a benchmark linear elasticity numerical example and a coupled steady poroelastic deformation problem, for which analytical solutions are known. Highly accurate solutions are obtained in each case, and convergence rates in excess of sixth-order are observed

The observed M−σM - \sigma relations imply that SMBHs grow by cold chaotic accretion

We argue that current observations of $M - \sigma$ relations for galaxies can be used to constrain theories of super-massive black holes (SMBH) feeding. In particular, assuming that SMBH mass is limited only by the feedback on the gas that feeds it, we show that SMBHs fed via a planar galaxy scale gas flow, such as a disc or a bar, should be much more massive than their counterparts fed by quasi-spherical inflows. This follows from the relative inefficiency of AGN feedback on a flattened inflow. We find that even under the most optimistic conditions for SMBH feedback on flattened inflows, the mass at which the SMBH expels the gas disc and terminates its own growth is a factor of several higher than the one established for quasi-spherical inflows. Any beaming of feedback away from the disc and any disc self-shadowing strengthens this result further. Contrary to this theoretical expectation, recent observations have shown that SMBH in pseudobulge galaxies (which are associated with barred galaxies) are typically under- rather than over-massive when compared with their classical bulge counterparts at a fixed value of $\sigma$. We conclude from this that SMBHs are not fed by large (100 pc to many kpc) scale gas discs or bars, most likely because such planar flows are turned into stars too efficiently to allow any SMBH growth. Based on this and other related observational evidence, we argue that most SMBHs grow by chaotic accretion of gas clouds with a small and nearly randomly distributed direction of angular momentum.Comment: 8 pages; submitted to ApJ; version that takes referee's comments into accoun

Feeding supermassive black holes through supersonic turbulence and ballistic accretion

It has long been recognized that the main obstacle to the accretion of gas on to supermassive black holes (SMBHs) is a large specific angular momentum. It is feared that the gas settles in a large-scale disc, and that accretion would then proceed too inefficiently to explain the masses of the observed SMBHs. Here we point out that, while the mean angular momentum in the bulge is very likely to be large, the deviations from the mean can also be significant. Indeed, cosmological simulations show that velocity and angular momentum fields of gas flows on to galaxies are very complex. Furthermore, inside bulges the gas velocity distribution can be further randomized by the velocity kicks due to feedback from star formation. We perform hydrodynamical simulations of gaseous rotating shells infalling on to an SMBH, attempting to quantify the importance of velocity dispersion in the gas at relatively large distances from the black hole. We implement this dispersion by means of a supersonic turbulent velocity spectrum. We find that, while in the purely rotating case the circularization process leads to efficient mixing of gases with different angular momenta, resulting in a low accretion rate, the inclusion of turbulence increases this accretion rate by up to several orders of magnitude. We show that this can be understood based on the notion of ‘ballistic' accretion, whereby dense filaments, created by convergent turbulent flows, travel through the ambient gas largely unaffected by hydrodynamical drag. This prevents the efficient gas mixing that was found in the simulations without turbulence, and allows a fraction of gas to impact the innermost boundary of the simulations directly. Using the ballistic approximation, we derive a simple analytical formula that captures the numerical results to within a factor of a few. Rescaling our results to astrophysical bulges, we argue that this ‘ballistic' mode of accretion could provide the SMBHs with sufficient fuel without the need to channel the gas via large-scale discs or bars. We therefore argue that star formation in bulges can be a strong catalyst for SMBH accretio

Private education and disadvantage: the experiences of assisted place holders

It is now nearly thirty years since Margaret Thatcher and her Conservative administration introduced the Assisted Places Scheme (their first education policy) and over ten years since New Labour abolished it. The Scheme, which was designed to provide a ladder of opportunity for academically able students from poor backgrounds to attend private schools, is of more than historical interest. It can be used to illuminate enduring sociological concerns about the relationship between home and school. This paper draws on retrospective interview data to reveal how the Scheme was experienced by its more disadvantaged beneficiaries. Revisiting classic sociological analyses from the 1960s and 1970s, it unravels the complex interactions between home background, friendship networks and school cultures and shows how these contributed to contrasting experiences of commitment, detachment, estrangement and alienation. These differing modes of engagement with schooling appear to have had lasting effects on our respondents and influenced their subsequent careers and orientations

Migratory bird species benefit from traditional agricultural gardens in arid South Sinai

In temperate and tropical regions agricultural conversion of natural habitat typically has negative impacts upon the diversity and functional complexity of bird communities. In arid environments however, the irrigation associated with agricultural can lead to an increase in local abundances of plant and insect resources, so has the potential to benefit bird communities. South Sinai is a key migratory corridor for many birds making the annual journey from wintering sites in Africa to breeding sites in Europe. We assess the importance of traditional Bedouin agricultural gardens for both resident and migratory species by comparing the density and functional composition of birds within the irrigated gardens to those in the unmanaged desert habitat. Estimated bird densities were significantly higher within the gardens than the unmanaged habitat, with a higher estimated species richness within the gardens. Functional composition of bird communities differed between the two habitats, with gardens supporting a higher proportion of insectivorous and migratory birds in addition to the resident desert species that were associated with the unmanaged habitat. Migratory species were almost entirely absent from the unmanaged habitat, suggesting that this region may not be used as a migratory stop-off if not for the presence of traditional agricultural gardens

Modelling supermassive black hole growth: towards an improved sub‐grid prescription

Accretion on to supermassive black holes (SMBHs) in galaxy formation simulations is frequently modelled by the Bondi-Hoyle formalism. Here we examine the validity of this approach analytically and numerically. We argue that the character of the flow where one evaluates the gas properties is unlikely to satisfy the simple Bondi-Hoyle model. Only in the specific case of hot virialized gas with zero angular momentum and negligible radiative cooling is the Bondi-Hoyle solution relevant. In the opposite extreme, where the gas is in a state of free‐fall at the evaluation radius due to efficient cooling and the dominant gravity of the surrounding halo, the Bondi-Hoyle formalism can be erroneous by orders of magnitude in either direction. This may impose artificial trends with halo mass in cosmological simulations by being wrong by different factors for different halo masses. We propose an expression for the sub‐grid accretion rate which interpolates between the free‐fall regime and the Bondi-Hoyle regime, therefore taking account of the contribution of the halo to the gas dynamic

Comparison of Balloonsonde and Remote Sensing Atmospheric Measurements

As part of its aircraft icing research program, the NASA Glenn Research Center is conducting a program to develop technologies for the remote sensing of atmospheric conditions. A suite of instruments, currently ground-based, are used to identify a region of supercooled liquid water which is labeled as hazardous if its liquid water content is sufficiently high. During the recently completed Alliance Icing Research Study (AIRS II), these instruments were deployed in conjunction with those of other U.S. and Canadian researchers at the Mirabel Airport near Montreal. As part of the study, balloonsondes were employed to provide in-situ measurement of the atmospheric conditions that were being concurrently remotely sensed. Balloonsonde launches occurred daily at 1200 GMT to provide AIRS forecasters with local data and additionally when research aircraft were present in the airspace. In this paper, we compare the processed data from the NASA remote sensing instruments, which included an X-band radar, lidar and two radiometers, to the data gathered from the 70 soundings conducted while the NASA instruments were active. Among the parameters compared are cloud upper and lower boundaries, temperature and humidity profiles and freezing levels