Systematic Analysis of Duplications and Deletions in the Malaria Parasite P. falciparum: A Dissertation

Duplications and deletions are a major source of genomic variation. Duplications, specifically, have a significant impact on gene genesis and dosage, and the malaria parasite P. falciparum has developed resistance to a growing number of anti-malarial drugs via gene duplication. It also contains highly duplicated families of antigenically variable allelic genes. While specific genes and families have been studied, a comprehensive analysis of duplications and deletions within the reference genome and population has not been performed. We analyzed the extent of segmental duplications (SD) in the reference genome for P. falciparum, primarily by a whole genome self alignment. We discovered that while 5% of the genome identified as SD, the distribution within the genome was partition clustered, with the vast majority localized to the subtelomeres. Within the SDs, we found an overrepresentation of genes encoding antigenically diverse proteins exposed to the extracellular membrane, specifically the var, rifin, and stevor gene families. To examine variation of duplications and deletions within the parasite populations, we designed a novel computational methodology to identify copy number variants (CNVs) from high throughput sequencing, using a read depth based approach refined with discordant read pairs. After validating the program against in vitro lab cultures, we analyzed isolates from Senegal for initial tests into clinical isolates. We then expanded our search to a global sample of 610 strains from Africa and South East Asia, identifying 68 CNV regions. Geographically, genic CNV were found on average in less than 10% of the population, indicating that CNV are rare. However, CNVs at high frequency were almost exclusively duplications associated with known drug resistant CNVs. We also identified the novel biallelic duplication of the crt gene – containing both the chloroquine resistant and sensitive allele. The synthesis of our SD and CNV analysis indicates a CNV conservative P. falciparum genome except where drug and human immune pressure select for gene duplication

Encouraging the perceptual underdog: positive affective priming of nonpreferred local–global processes

Two experiments examined affective priming of global and local perception. Participants attempted to detect a target that might be present as either a global or a local shape. Verbal primes were used in 1 experiment, and pictorial primes were used in the other. In both experiments, positive primes led to improved performance on the nonpreferred dimension. For participants exhibiting global precedence, detection of local targets was significantly improved, whereas for participants exhibiting local precedence, detection of global targets was significantly improved. The results provide support for an interpretation of the effects of positive affective priming in terms of increased perceptual flexibility

Diffractive deeply inelastic scattering of hadronic states with small transverse size

Diffractive deeply inelastic scattering from a hadron is described in terms of diffractive quark and gluon distributions. If the transverse size of the hadronic state is sufficiently small, these distributions are calculable using perturbation theory. We present such a calculation and discuss the underlying dynamics. We comment on the relation between this dynamics and the pattern of scaling violation observed in the hard diffraction of large-size states at HERA.Comment: 8 pages including 3 figures, REVTE

Multiplicities for LHC Nuclear Collisions Using HERA Structure Functions

We compute in QCD perturbation theory the transverse energy carried by gluons, quarks and antiquarks with $p_T\ge p_0\approx 2$ GeV in Pb+Pb collisions at $\sqrt{s}=5500$ $A$GeV by using structure functions compatible with the small-$x$ increase observed at HERA. This gives a perturbative estimate for the energy and entropy density of the bulk system at times $\tau\sim 0.1$ fm. The predicted initial gluon entropy density gives a lower limit of about 2200...3400 for the final charged multiplicity. Sources of further entropy increase are discussed.Comment: HU-TFT-94-6, 7 pages, 3 PostScript figures included in the end of the tex-fil

DNA-Damage-Induced Differentiation in Hematopoietic Stem Cells

Aging of hematopoietic stem cells (HSCs) is accompanied by diminished functional potential. Wang et al. now provide evidence for an HSC-specific differentiation checkpoint mediated by the transcription factor BATF, which limits self-renewal of HSCs in response to the accumulation of DNA damage

Diffractive Phenomena and Shadowing in Deep-Inelastic Scattering

Shadowing effects in deep-inelastic lepton-nucleus scattering probe the mass spectrum of diffractive leptoproduction from individual nucleons. We explore this relationship using current experimental information on both processes. In recent data from the NMC and E665 collaboration, taken at small x << 0.1 and Q^2 < 1 GeV^2, shadowing is dominated by the diffractive excitation and coherent interaction of low mass vector mesons. If shadowing is explored at small x > 1 GeV^2 as discussed at HERA, the situation is different. Here dominant contributions come from the coherent interaction of diffractively produced heavy mass states. Furthermore we observe that the energy dependence of shadowing is directly related to the mass dependence of the diffractive production cross section for free nucleon targets.Comment: 12 pages Latex, 8 figure