Spatiotemporal PET reconstruction using ML-EM with learned diffeomorphic deformation

Patient movement in emission tomography deteriorates reconstruction quality because of motion blur. Gating the data improves the situation somewhat: each gate contains a movement phase which is approximately stationary. A standard method is to use only the data from a few gates, with little movement between them. However, the corresponding loss of data entails an increase of noise. Motion correction algorithms have been implemented to take into account all the gated data, but they do not scale well, especially not in 3D. We propose a novel motion correction algorithm which addresses the scalability issue. Our approach is to combine an enhanced ML-EM algorithm with deep learning based movement registration. The training is unsupervised, and with artificial data. We expect this approach to scale very well to higher resolutions and to 3D, as the overall cost of our algorithm is only marginally greater than that of a standard ML-EM algorithm. We show that we can significantly decrease the noise corresponding to a limited number of gates

The Caenorhabditis chemoreceptor gene families

Background: Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results: Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion: Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.JHT was supported by NIH grant RO1GM48700 and HMR by R01AI56081

A reverse engineering approach to the suppression of citation biases reveals universal properties of citation distributions

The large amount of information contained in bibliographic databases has recently boosted the use of citations, and other indicators based on citation numbers, as tools for the quantitative assessment of scientific research. Citations counts are often interpreted as proxies for the scientific influence of papers, journals, scholars, and institutions. However, a rigorous and scientifically grounded methodology for a correct use of citation counts is still missing. In particular, cross-disciplinary comparisons in terms of raw citation counts systematically favors scientific disciplines with higher citation and publication rates. Here we perform an exhaustive study of the citation patterns of millions of papers, and derive a simple transformation of citation counts able to suppress the disproportionate citation counts among scientific domains. We find that the transformation is well described by a power-law function, and that the parameter values of the transformation are typical features of each scientific discipline. Universal properties of citation patterns descend therefore from the fact that citation distributions for papers in a specific field are all part of the same family of univariate distributions.Comment: 9 pages, 6 figures. Supporting information files available at http://filrad.homelinux.or

Floral temperature and optimal foraging: is heat a feasible floral reward for pollinators?

As well as nutritional rewards, some plants also reward ectothermic pollinators with warmth. Bumble bees have some control over their temperature, but have been shown to forage at warmer flowers when given a choice, suggesting that there is some advantage to them of foraging at warm flowers (such as reducing the energy required to raise their body to flight temperature before leaving the flower). We describe a model that considers how a heat reward affects the foraging behaviour in a thermogenic central-place forager (such as a bumble bee). We show that although the pollinator should spend a longer time on individual flowers if they are warm, the increase in total visit time is likely to be small. The pollinator's net rate of energy gain will be increased by landing on warmer flowers. Therefore, if a plant provides a heat reward, it could reduce the amount of nectar it produces, whilst still providing its pollinator with the same net rate of gain. We suggest how heat rewards may link with plant life history strategies

Onset dynamics of type A botulinum neurotoxin-induced paralysis

Experimental studies have demonstrated that botulinum neurotoxin serotype A (BoNT/A) causes flaccid paralysis by a multi-step mechanism. Following its binding to specific receptors at peripheral cholinergic nerve endings, BoNT/A is internalized by receptor-mediated endocytosis. Subsequently its zinc-dependent catalytic domain translocates into the neuroplasm where it cleaves a vesicle-docking protein, SNAP-25, to block neurally evoked cholinergic neurotransmission. We tested the hypothesis that mathematical models having a minimal number of reactions and reactants can simulate published data concerning the onset of paralysis of skeletal muscles induced by BoNT/A at the isolated rat neuromuscular junction (NMJ) and in other systems. Experimental data from several laboratories were simulated with two different models that were represented by sets of coupled, first-order differential equations. In this study, the 3-step sequential model developed by Simpson (J Pharmacol Exp Ther 212:16–21,1980) was used to estimate upper limits of the times during which anti-toxins and other impermeable inhibitors of BoNT/A can exert an effect. The experimentally determined binding reaction rate was verified to be consistent with published estimates for the rate constants for BoNT/A binding to and dissociating from its receptors. Because this 3-step model was not designed to reproduce temporal changes in paralysis with different toxin concentrations, a new BoNT/A species and rate (kS) were added at the beginning of the reaction sequence to create a 4-step scheme. This unbound initial species is transformed at a rate determined by kS to a free species that is capable of binding. By systematically adjusting the values of kS, the 4-step model simulated the rapid decline in NMJ function (kS ≥0.01), the less rapid onset of paralysis in mice following i.m. injections (kS = 0.001), and the slow onset of the therapeutic effects of BoNT/A (kS < 0.001) in man. This minimal modeling approach was not only verified by simulating experimental results, it helped to quantitatively define the time available for an inhibitor to have some effect (tinhib) and the relation between this time and the rate of paralysis onset. The 4-step model predicted that as the rate of paralysis becomes slower, the estimated upper limits of (tinhib) for impermeable inhibitors become longer. More generally, this modeling approach may be useful in studying the kinetics of other toxins or viruses that invade host cells by similar mechanisms, e.g., receptor-mediated endocytosis

A Gammaherpesviral Internal Repeat Contributes to Latency Amplification

BACKGROUND: Gammaherpesviruses cause important infections of humans, in particular in immunocompromised patients. The genomes of gammaherpesviruses contain variable numbers of internal repeats whose precise role for in vivo pathogenesis is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We used infection of laboratory mice with murine gammaherpesvirus 68 (MHV-68) to explore the biological role of the 40 bp internal repeat of MHV-68. We constructed several mutant viruses partially or completely lacking this repeat. Both in vitro and in vivo, the loss of the repeat did not substantially affect lytic replication of the mutant viruses. However, the extent of splenomegaly, which is associated with the establishment of latency, and the number of ex vivo reactivating and genome positive splenocytes were reduced. Since the 40 bp repeat is part of the hypothetical open reading frame (ORF) M6, it might function as part of M6 or as an independent structure. To differentiate between these two possibilities, we constructed an N-terminal M6STOP mutant, leaving the repeat structure intact but rendering ORF M6 unfunctional. Disruption of ORF M6 did neither affect lytic nor latent infection. In contrast to the situation in lytically infected NIH3T3 cells, the expression of the latency-associated genes K3 and ORF72 was reduced in the latently infected murine B cell line Ag8 in the absence of the 40 bp repeat. CONCLUSIONS/SIGNIFICANCE: These data suggest that the 40 bp repeat contributes to latency amplification and might be involved in the regulation of viral gene expression

Stochastic population growth in spatially heterogeneous environments

Classical ecological theory predicts that environmental stochasticity increases extinction risk by reducing the average per-capita growth rate of populations. To understand the interactive effects of environmental stochasticity, spatial heterogeneity, and dispersal on population growth, we study the following model for population abundances in $n$ patches: the conditional law of $X_{t+dt}$ given $X_t=x$ is such that when $dt$ is small the conditional mean of $X_{t+dt}^i-X_t^i$ is approximately $[x^i\mu_i+\sum_j(x^j D_{ji}-x^i D_{ij})]dt$, where $X_t^i$ and $\mu_i$ are the abundance and per capita growth rate in the $i$-th patch respectivly, and $D_{ij}$ is the dispersal rate from the $i$-th to the $j$-th patch, and the conditional covariance of $X_{t+dt}^i-X_t^i$ and $X_{t+dt}^j-X_t^j$ is approximately $x^i x^j \sigma_{ij}dt$. We show for such a spatially extended population that if $S_t=(X_t^1+...+X_t^n)$ is the total population abundance, then $Y_t=X_t/S_t$, the vector of patch proportions, converges in law to a random vector $Y_\infty$ as $t\to\infty$, and the stochastic growth rate $\lim_{t\to\infty}t^{-1}\log S_t$ equals the space-time average per-capita growth rate \sum_i\mu_i\E[Y_\infty^i] experienced by the population minus half of the space-time average temporal variation \E[\sum_{i,j}\sigma_{ij}Y_\infty^i Y_\infty^j] experienced by the population. We derive analytic results for the law of $Y_\infty$, find which choice of the dispersal mechanism $D$ produces an optimal stochastic growth rate for a freely dispersing population, and investigate the effect on the stochastic growth rate of constraints on dispersal rates. Our results provide fundamental insights into "ideal free" movement in the face of uncertainty, the persistence of coupled sink populations, the evolution of dispersal rates, and the single large or several small (SLOSS) debate in conservation biology.Comment: 47 pages, 4 figure

On the interpretation of a possible ∼ 750 GeV particle decaying into γγ

We consider interpretations of the recent ∼ 3σ reports by the CMS and ATLAS collaborations of a possible X (∼750 GeV) state decaying into γγ final states. We focus on the possibilities that this is a scalar or pseudoscalar electroweak isoscalar state produced by gluon-gluon fusion mediated by loops of heavy fermions. We consider several models for these fermions, including a single vector-like charge 2/3 T quark, a doublet of vector-like quarks (T, B), and a vector-like generation of quarks, with or without leptons that also contribute to the X → γγ decay amplitude. We also consider the possibility that X (750) is a dark matter mediator, with a neutral vector-like dark matter particle. These scenarios are compatible with the present and prospective direct limits on vector-like fermions from LHC Runs 1 and 2, as well as indirect constraints from electroweak precision measurements, and we show that the required Yukawa-like couplings between the X particle and the heavy vector-like fermions are small enough to be perturbative so long as the X particle has dominant decay modes into gg and γγ. The decays X → ZZ, Zγ and W+W− are interesting prospective signatures that may help distinguish between different vector-like fermion scenarios

Inclusive J/ψ production at mid-rapidity in pp collisions at √s = 5.02 TeV

Inclusive J/ψ production is studied in minimum-bias proton-proton collisions at a centre-of-mass energy of s = 5.02 TeV by ALICE at the CERN LHC. The measurement is performed at mid-rapidity (|y| &lt; 0.9) in the dielectron decay channel down to zero transverse momentum pT, using a data sample corresponding to an integrated luminosity of Lint = 19.4 ± 0.4 nb−1. The measured pT-integrated inclusive J/ψ production cross sec- tion is dσ/dy = 5.64 ± 0.22(stat.) ± 0.33(syst.) ± 0.12(lumi.) μb. The pT-differential cross section d2σ/dpTdy is measured in the pT range 0–10 GeV/c and compared with state-of- the-art QCD calculations. The J/ψ 〈pT〉 and 〈pT2〉 are extracted and compared with results obtained at other collision energies. [Figure not available: see fulltext.]

Measurement of Λ (1520) production in pp collisions at √s=7TeV and p–Pb collisions at √sNN=5.02TeV

The production of the Λ (1520) baryonic resonance has been measured at midrapidity in inelastic pp collisions at s=7TeV and in p–Pb collisions at sNN=5.02TeV for non-single diffractive events and in multiplicity classes. The resonance is reconstructed through its hadronic decay channel Λ (1520) → pK - and the charge conjugate with the ALICE detector. The integrated yields and mean transverse momenta are calculated from the measured transverse momentum distributions in pp and p–Pb collisions. The mean transverse momenta follow mass ordering as previously observed for other hyperons in the same collision systems. A Blast-Wave function constrained by other light hadrons (π, K, KS0, p, Λ) describes the shape of the Λ (1520) transverse momentum distribution up to 3.5GeV/c in p–Pb collisions. In the framework of this model, this observation suggests that the Λ (1520) resonance participates in the same collective radial flow as other light hadrons. The ratio of the yield of Λ (1520) to the yield of the ground state particle Λ remains constant as a function of charged-particle multiplicity, suggesting that there is no net effect of the hadronic phase in p–Pb collisions on the Λ (1520) yield