Real-time PCR assays for detection and quantification of early P. falciparum gametocyte stages

Introduction The use of reverse transcription, quantitative qRT-PCR assays for detection and quantification of late gametocyte stages has revealed the high transmission capacity of the human malaria parasite, Plasmodium falciparum. A full understanding how the parasite adjusts its transmission in response to varying in-host environmental conditions during natural infections requires simultaneous quantification of early and late gametocytes. Here, we describe qRT-PCR assays that are specific for detection and quantification of early-stage gametocytes of P. falciparum. Methods The assays are based on expression of known early gametocyte genes (pfpeg4, pfg27, pfge1, pfge3 and pfgexp5). The specificity of the qRT-PCR assays was tested using purified stage II and stage V gametocytes. These validated assays were used with qRT-PCR assays targeting late stage (pfs25) and all-stage (pfs16) gametocyte-specific transcripts to quantify gametocytes in natural P. falciparum infections and in a controlled human clinical infection study. Results The relative expression of pfpeg4, pfg27 and pfge3, but not of pfge1 and pfgexp5, was significantly higher in purified stage II compared to stage V gametocytes, indicating early gametocyte specificity. In natural infections, 71.2% of individuals had both early and late gametocyte transcripts (pfpeg4/pfg27 plus pfs25), 12.6% harboured only early gametocytes transcripts (pfpeg4/pfg27), and 15.2% had only late gametocytes transcripts (pfs25). In natural infections, the limit of detection was equivalent to 190 and 390 gametocytes/mL blood for pfpeg4 and pfg27, respectively. In infected volunteers, transcripts of pfpeg4 and pfg27 were detected shortly after the onset of blood stage infection, demonstrating the specificity of the assays. Conclusion The pfpeg4 and pfg27 qRT-PCR assays can be used specifically to quantify circulating immature gametocytes. Quantification of early gametocytes will improve understanding of epidemiological processes that modulate P. falciparum transmission and enhance the evaluation of transmission blocking interventions

Low-Temperature Specific Heat of an Extreme-Type-II Superconductor at High Magnetic Fields

We present a detailed study of the quasiparticle contribution to the low-temperature specific heat of an extreme type-II superconductor at high magnetic fields. Within a T-matrix approximation for the self-energies in the mixed state of a homogeneous superconductor, the electronic specific heat is a linear function of temperature with a linear-$T$ coefficient $\gamma_s(H)$ being a nonlinear function of magnetic field $H$. In the range of magnetic fields H\agt (0.15-0.2)H_{c2} where our theory is applicable, the calculated $\gamma_s(H)$ closely resembles the experimental data for the borocarbide superconductor YNi$_2$B$_2$C.Comment: 7 pages, 2 figures, to appear in Physical Review

Has the evolution of complexity in the amphibian papilla influenced anuran speciation rates?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72375/1/j.1420-9101.2006.01079.x.pd

SuperWIMP Dark Matter Signals from the Early Universe

Cold dark matter may be made of superweakly-interacting massive particles, superWIMPs, that naturally inherit the desired relic density from late decays of metastable WIMPs. Well-motivated examples are weak-scale gravitinos in supergravity and Kaluza-Klein gravitons from extra dimensions. These particles are impossible to detect in all dark matter experiments. We find, however, that superWIMP dark matter may be discovered through cosmological signatures from the early universe. In particular, superWIMP dark matter has observable consequences for Big Bang nucleosynthesis and the cosmic microwave background (CMB), and may explain the observed underabundance of 7Li without upsetting the concordance between deuterium and CMB baryometers. We discuss implications for future probes of CMB black body distortions and collider searches for new particles. In the course of this study, we also present a model-independent analysis of entropy production from late-decaying particles in light of WMAP data.Comment: 19 pages, 5 figures, typos correcte

Generalized Quantum Theory of Recollapsing Homogeneous Cosmologies

A sum-over-histories generalized quantum theory is developed for homogeneous minisuperspace type A Bianchi cosmological models, focussing on the particular example of the classically recollapsing Bianchi IX universe. The decoherence functional for such universes is exhibited. We show how the probabilities of decoherent sets of alternative, coarse-grained histories of these model universes can be calculated. We consider in particular the probabilities for classical evolution defined by a suitable coarse-graining. For a restricted class of initial conditions and coarse grainings we exhibit the approximate decoherence of alternative histories in which the universe behaves classically and those in which it does not. For these situations we show that the probability is near unity for the universe to recontract classically if it expands classically. We also determine the relative probabilities of quasi-classical trajectories for initial states of WKB form, recovering for such states a precise form of the familiar heuristic "J d\Sigma" rule of quantum cosmology, as well as a generalization of this rule to generic initial states.Comment: 41 pages, 4 eps figures, revtex 4. Modest revisions throughout. Physics unchanged. To appear in Phys. Rev.

Quenched charmonium spectrum

We study charmonium using the standard relativistic formalism in the quenched approximation, on a set of lattices with isotropic lattice spacings ranging from 0.1 to 0.04 fm. We concentrate on the calculation of the hyperfine splitting between eta_c and J/psi, aiming for a controlled continuum extrapolation of this quantity. The splitting extracted from the non-perturbatively improved clover Dirac operator shows very little dependence on the lattice spacing for $a \leq 0.1$ fm. The dependence is much stronger for Wilson and tree-level improved clover operators, but they still yield consistent extrapolations if sufficiently fine lattices, $a \leq 0.07$ fm ($a M(\eta_c) \leq 1$), are used. Our result for the hyperfine splitting is 77(2)(6) MeV (where Sommer's parameter, r_0, is used to fix the scale). This value remains about 30% below experiment. Dynamical fermions and OZI-forbidden diagrams both contribute to the remainder. Results for the eta_c and J/psi wave functions are also presented.Comment: 22 pages, 7 figure

Forgiveness and the Need to Belong

People who experience a strong need to belong might be particularly inclined to forgive wrongdoings to preserve social bonds. Three studies that utilized different methods and measures of forgiveness consistently demonstrated this is not the case. The authors found that individuals high in the need to belong report practicing forgiveness with less frequency and value it no more than those low in the need to belong (Study 1). In Study 2, they found that satisfying the need to belong led participants to express greater willingness to forgive hypothetical offenses compared to participants in a control group. Finally, in Study 3, the authors linked the need to belong to forgiveness of specific transgressions and found that this negative relationship was mediated by offense-related anger and perceptions of offense severity. These findings suggest that needing to belong paradoxically interferes with forgiveness, even though forgiving could promote the satisfaction of belongingness needs following transgressions.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types