The stochastic quasi-steady-state assumption: Reducing the model but not the noise

Highly reactive species at small copy numbers play an important role in many biological reaction networks. We have described previously how these species can be removed from reaction networks using stochastic quasi-steady-state singular perturbation analysis (sQSPA). In this paper we apply sQSPA to three published biological models: the pap operon regulation, a biochemical oscillator, and an intracellular viral infection. These examples demonstrate three different potential benefits of sQSPA. First, rare state probabilities can be accurately estimated from simulation. Second, the method typically results in fewer and better scaled parameters that can be more readily estimated from experiments. Finally, the simulation time can be significantly reduced without sacrificing the accuracy of the solution

Electronic screening and damping in magnetars

We calculate the screening of the ion-ion potential due to electrons in the presence of a large background magnetic field, at densities of relevance to neutron star crusts. Using the standard approach to incorporate electron screening through the one-loop polarization function, we show that the magnetic field produces important corrections both at short and long distances. In extreme fields, realized in highly magnetized neutron stars called magnetars, electrons occupy only the lowest Landau levels in the relatively low density region of the crust. Here our results show that the screening length for Coulomb interactions between ions can be smaller than the inter-ion spacing. More interestingly, we find that the screening is anisotropic and the screened potential between two static charges exhibits long range Friedel oscillations parallel to the magnetic field. This long-range oscillatory behavior is likely to affect the lattice structure of ions, and can possibly create rod-like structures in the magnetar crusts. We also calculate the imaginary part of the electron polarization function which determines the spectrum of electron-hole excitations and plays a role in damping lattice phonon excitations. We demonstrate that even for modest magnetic fields this damping is highly anisotropic and will likely lead to anisotropic phonon heat transport in the outer neutron star crust.Comment: 14 pages, 5 Figure

Efficient Photon Coupling from a Diamond Nitrogen Vacancy Centre by Integration with Silica Fibre

A central goal in quantum information science is to efficiently interface photons with single optical modes for quantum networking and distributed quantum computing. Here, we introduce and experimentally demonstrate a compact and efficient method for the low-loss coupling of a solid-state qubit, the nitrogen vacancy (NV) centre in diamond, with a single-mode optical fibre. In this approach, single-mode tapered diamond waveguides containing exactly one high quality NV memory are selected and integrated on tapered silica fibres. Numerical optimization of an adiabatic coupler indicates that near-unity-efficiency photon transfer is possible between the two modes. Experimentally, we find an overall collection efficiency between 18-40 % and observe a raw single photon count rate above 700 kHz. This integrated system enables robust, alignment-free, and efficient interfacing of single-mode optical fibres with single photon emitters and quantum memories in solids

A Mean Field Analysis of Pairing in Asymmetric Fermi Systems at Finite Temperature

We study the phase diagram of a two component Fermi system with a weak attractive interaction. Our analysis includes the leading order Hartree energy shifts and pairing correlations at finite temperature and chemical potential difference between the two fermion species. We show that in an asymmetric system, the Hartree shift to the single particle energies are important for the phase competition between normal and superfluid phase and can change the phase transition curve qualitatively. At large asymmetry we find that a novel but somewhat fragile superfluid state can be favored due to finite temperature effects. We also investigate the transition between the normal phase and an inhomogeneous superfluid phase to study how gradient instabilities evolve with temperature and asymmetry. Finally, we adopt our analysis to study the density profiles of similar asymmetric Fermi systems that are being observed in cold atom experiments.Comment: 17 pages, 7 figure

A low energy theory for superfluid and solid matter and its application to the neutron star crust

We formulate a low energy effective theory describing phases of matter that are both solid and superfluid. These systems simultaneously break translational symmetry and the phase symmetry associated with particle number. The symmetries restrict the combinations of terms that can appear in the effective action and the lowest order terms featuring equal number of derivatives and Goldstone fields are completely specified by the thermodynamic free energy, or equivalently by the long-wavelength limit of static correlation functions in the ground state. We show that the underlying interaction between particles that constitute the lattice and the superfluid gives rise to entrainment, and mixing between the Goldstone modes. As a concrete example we discuss the low energy theory for the inner crust of a neutron star, where a lattice of ionized nuclei coexists with a neutron superfluid.Comment: 21 pages, 1 figur

Pathological and molecular evaluation of pancreatic neoplasms

Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from the molecular and genetic perspectives

A universal reference sample derived from clone vector for improved detection of differential gene expression

BACKGROUND: Using microarrays by co-hybridizing two samples labeled with different dyes enables differential gene expression measurements and comparisons across slides while controlling for within-slide variability. Typically one dye produces weaker signal intensities than the other often causing signals to be undetectable. In addition, undetectable spots represent a large problem for two-color microarray designs and most arrays contain at least 40% undetectable spots even when labeled with reference samples such as Stratagene's Universal Reference RNAs™. RESULTS: We introduce a novel universal reference sample that produces strong signal for all spots on the array, increasing the average fraction of detectable spots to 97%. Maximizing detectable spots on the reference image channel also decreases the variability of microarray data allowing for reliable detection of smaller differential gene expression changes. The reference sample is derived from sequence contained in the parental EST clone vector pT7T3D-Pac and is called vector RNA (vRNA). We show that vRNA can also be used for quality control of microarray printing and PCR product quality, detection of hybridization anomalies, and simplification of spot finding and segmentation tasks. This reference sample can be made inexpensively in large quantities as a renewable resource that is consistent across experiments. CONCLUSION: Results of this study show that vRNA provides a useful universal reference that yields high signal for almost all spots on a microarray, reduces variation and allows for comparisons between experiments and laboratories. Further, it can be used for quality control of microarray printing and PCR product quality, detection of hybridization anomalies, and simplification of spot finding and segmentation tasks. This type of reference allows for detection of small changes in differential expression while reference designs in general allow for large-scale multivariate experimental designs. vRNA in combination with reference designs enable systems biology microarray experiments of small physiologically relevant changes

Ternatin and improved synthetic variants kill cancer cells by targeting the elongation factor-1A ternary complex.

Cyclic peptide natural products have evolved to exploit diverse protein targets, many of which control essential cellular processes. Inspired by a series of cyclic peptides with partially elucidated structures, we designed synthetic variants of ternatin, a cytotoxic and anti-adipogenic natural product whose molecular mode of action was unknown. The new ternatin variants are cytotoxic toward cancer cells, with up to 500-fold greater potency than ternatin itself. Using a ternatin photo-affinity probe, we identify the translation elongation factor-1A ternary complex (eEF1A·GTP·aminoacyl-tRNA) as a specific target and demonstrate competitive binding by the unrelated natural products, didemnin and cytotrienin. Mutations in domain III of eEF1A prevent ternatin binding and confer resistance to its cytotoxic effects, implicating the adjacent hydrophobic surface as a functional hot spot for eEF1A modulation. We conclude that the eukaryotic elongation factor-1A and its ternary complex with GTP and aminoacyl-tRNA are common targets for the evolution of cytotoxic natural products

Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis.

OBJECTIVES: Tuberculosis (TB) is estimated to be the leading cause of HIV-related deaths globally. However, since HIV-associated TB frequently remains unascertained, we systematically reviewed autopsy studies to determine the true burden of TB at death. METHODS: We systematically searched Medline and Embase databases (to end 2013) for literature reporting on health facility-based autopsy studies of HIV-infected adults and/or children in resource-limited settings. Using forest plots and random-effects meta-analysis, we summarized the TB prevalence found at autopsy and used meta-regression to explore variables associated with autopsy TB prevalence. RESULTS: We included 36 eligible studies, reporting on 3237 autopsies. Autopsy TB prevalence was extremely heterogeneous (range 0-64.4%), but was markedly higher in adults [pooled prevalence 39.7%, 95% confidence interval (CI) 32.4-47.0%] compared to children (pooled prevalence 4.5%, 95% CI 1.7-7.4%). Post-mortem TB prevalence varied by world region, with pooled estimates in adults of 63.2% (95% CI 57.7-68.7%) in South Asia (n = 2 studies); 43.2% (95% CI 38.0-48.3) in sub-Saharan Africa (n = 9 studies); and 27.1% (95% CI 16.0-38.1%) in the Americas (n = 5 studies). Autopsy prevalence positively correlated with contemporary estimates of national TB prevalence. TB in adults was disseminated in 87.9% (82.2-93.7%) of cases and was considered the cause of death in 91.4% (95% CI 85.8-97.0%) of TB cases. Overall, TB was the cause of death in 37.2% (95% CI 25.7-48.7%) of adult HIV/AIDS-related deaths. TB remained undiagnosed at death in 45.8% (95% CI 32.6-59.1%) of TB cases. CONCLUSIONS: In resource-limited settings, TB accounts for approximately 40% of facility-based HIV/AIDS-related adult deaths. Almost half of this disease remains undiagnosed at the time of death. These findings highlight the critical need to improve the prevention, diagnosis and treatment of HIV-associated TB globally