1,522 research outputs found

    Knockout studies reveal an important role of <i>plasmodium</i> lipoic acid protein ligase a1 for asexual blood stage parasite survival

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    Lipoic acid (LA) is a dithiol-containing cofactor that is essential for the function of a-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl): &lt;i&gt;N&lt;/i&gt;-octanoyl (lipoyl) transferase (LipB) or lipoic acid protein ligases (LplA). Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that &lt;i&gt;LplA1&lt;/i&gt; plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite &lt;i&gt;P.falciparum&lt;/i&gt; consistently were unsuccessful while in the rodent malaria model parasite &lt;i&gt;P. berghei&lt;/i&gt; the &lt;i&gt;LplA1&lt;/i&gt; gene locus was targeted by knock-in and knockout constructs. However, the &lt;i&gt;LplA1&lt;/i&gt; &lt;sup&gt;(-)&lt;/sup&gt; mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite

    De-Trending Time Series for Astronomical Variability Surveys

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    We present a de-trending algorithm for the removal of trends in time series. Trends in time series could be caused by various systematic and random noise sources such as cloud passages, changes of airmass, telescope vibration or CCD noise. Those trends undermine the intrinsic signals of stars and should be removed. We determine the trends from subsets of stars that are highly correlated among themselves. These subsets are selected based on a hierarchical tree clustering algorithm. A bottom-up merging algorithm based on the departure from normal distribution in the correlation is developed to identify subsets, which we call clusters. After identification of clusters, we determine a trend per cluster by weighted sum of normalized light-curves. We then use quadratic programming to de-trend all individual light-curves based on these determined trends. Experimental results with synthetic light-curves containing artificial trends and events are presented. Results from other de-trending methods are also compared. The developed algorithm can be applied to time series for trend removal in both narrow and wide field astronomy.Comment: Revised version according to the referee's second revie

    Structural plasticity of the living kinetochore

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    The kinetochore is a large, evolutionarily conserved protein structure that connects chromosomes with microtubules. During chromosome segregation, outer kinetochore components track depolymerizing ends of microtubules to facilitate the separation of chromosomes into two cells. In budding yeast, each chromosome has a point centromere upon which a single kinetochore is built, which attaches to a single microtubule. This defined architecture facilitates quantitative examination of kinetochores during the cell cycle. Using three independent measures-calibrated imaging, FRAP, and photoconversion-we find that the Dam1 submodule is unchanged during anaphase, whereas MIND and Ndc80 submodules add copies to form an "anaphase configuration" kinetochore. Microtubule depolymerization and kinesin-related motors contribute to copy addition. Mathematical simulations indicate that the addition of microtubule attachments could facilitate tracking during rapid microtubule depolymerization. We speculate that the minimal kinetochore configuration, which exists from G1 through metaphase, allows for correction of misattachments. Our study provides insight into dynamics and plasticity of the kinetochore structure during chromosome segregation in living cells

    Dimensionality and dynamics in the behavior of C. elegans

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    A major challenge in analyzing animal behavior is to discover some underlying simplicity in complex motor actions. Here we show that the space of shapes adopted by the nematode C. elegans is surprisingly low dimensional, with just four dimensions accounting for 95% of the shape variance, and we partially reconstruct "equations of motion" for the dynamics in this space. These dynamics have multiple attractors, and we find that the worm visits these in a rapid and almost completely deterministic response to weak thermal stimuli. Stimulus-dependent correlations among the different modes suggest that one can generate more reliable behaviors by synchronizing stimuli to the state of the worm in shape space. We confirm this prediction, effectively "steering" the worm in real time.Comment: 9 pages, 6 figures, minor correction

    Dual-gated bilayer graphene hot electron bolometer

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    Detection of infrared light is central to diverse applications in security, medicine, astronomy, materials science, and biology. Often different materials and detection mechanisms are employed to optimize performance in different spectral ranges. Graphene is a unique material with strong, nearly frequency-independent light-matter interaction from far infrared to ultraviolet, with potential for broadband photonics applications. Moreover, graphene's small electron-phonon coupling suggests that hot-electron effects may be exploited at relatively high temperatures for fast and highly sensitive detectors in which light energy heats only the small-specific-heat electronic system. Here we demonstrate such a hot-electron bolometer using bilayer graphene that is dual-gated to create a tunable bandgap and electron-temperature-dependent conductivity. The measured large electron-phonon heat resistance is in good agreement with theoretical estimates in magnitude and temperature dependence, and enables our graphene bolometer operating at a temperature of 5 K to have a low noise equivalent power (33 fW/Hz1/2). We employ a pump-probe technique to directly measure the intrinsic speed of our device, >1 GHz at 10 K.Comment: 5 figure

    Age and Metallicity Distribution of the Galactic Bulge from Extensive Optical and Near-IR Stellar Photometry

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    We present a new determination of the metallicity distribution, age, and luminosity function of the Galactic bulge stellar population. By combining near-IR data from the 2MASS survey, from the SOFI imager at ESO NTT and the NICMOS camera on board HST we were able to construct color-magnitude diagrams (CMD) and luminosity functions (LF) with large statistics and small photometric errors from the Asymptotic Giant Branch (AGB) and Red Giant Branch (RGB) tip down to 0.15M\sim 0.15 M_\odot. This is the most extended and complete LF so far obtained for the galactic bulge. Similar near-IR data for a disk control field were used to decontaminate the bulge CMDs from foreground disk stars, and hence to set stronger constraint on the bulge age, which we found to be as large as that of Galactic globular clusters, or \gsim 10 Gyr. No trace is found for any younger stellar population. Synthetic CMDs have been constructed to simulate the effect of photometric errors, blending, differential reddening, metallicity dispersion and depth effect in the comparison with the observational data. By combining the near-IR data with optical ones, from the Wide Field Imager at the ESO/MPG 2.2m telescope, a disk-decontaminated (MK,VK)(M_K,V-K) CMD has been constructed and used to derive the bulge metallicity distribution, by comparison with empirical RGB templates. The bulge metallicity is found to peak at near solar value, with a sharp cutoff just above solar, and a tail towards lower metallicity that does not appreciably extend below [M/H]1.5\sim-1.5.Comment: 28 pages, 27 figures, A&A in press Full resolution version available at http://www.eso.org/~mzoccali/bulgepap

    Topological Color Codes and Two-Body Quantum Lattice Hamiltonians

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    Topological color codes are among the stabilizer codes with remarkable properties from quantum information perspective. In this paper we construct a four-valent lattice, the so called ruby lattice, governed by a 2-body Hamiltonian. In a particular regime of coupling constants, degenerate perturbation theory implies that the low energy spectrum of the model can be described by a many-body effective Hamiltonian, which encodes the color code as its ground state subspace. The gauge symmetry Z2×Z2\mathbf{Z}_{2}\times\mathbf{Z}_{2} of color code could already be realized by identifying three distinct plaquette operators on the lattice. Plaquettes are extended to closed strings or string-net structures. Non-contractible closed strings winding the space commute with Hamiltonian but not always with each other giving rise to exact topological degeneracy of the model. Connection to 2-colexes can be established at the non-perturbative level. The particular structure of the 2-body Hamiltonian provides a fruitful interpretation in terms of mapping to bosons coupled to effective spins. We show that high energy excitations of the model have fermionic statistics. They form three families of high energy excitations each of one color. Furthermore, we show that they belong to a particular family of topological charges. Also, we use Jordan-Wigner transformation in order to test the integrability of the model via introducing of Majorana fermions. The four-valent structure of the lattice prevents to reduce the fermionized Hamiltonian into a quadratic form due to interacting gauge fields. We also propose another construction for 2-body Hamiltonian based on the connection between color codes and cluster states. We discuss this latter approach along the construction based on the ruby lattice.Comment: 56 pages, 16 figures, published version

    Use of multicriteria decision analysis for assessing the benefit and risk of over-the-counter analgesics

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    Objectives To test the ability of a multicriteria decision analysis (MCDA) model to incorporate disparate data sources of varying quality along with clinical judgement in a benefit–risk assessment of six well-known pain-relief drugs. Methods Six over-the-counter (OTC) analgesics were evaluated against three favourable effects and eight unfavourable effects by seven experts who specialise in the relief of pain, two in a 2-day facilitated workshop whose input data and judgements were later peer-reviewed by five additional experts. Key findings Ibuprofen salts and solubilised emerged with the best benefit–risk profile, followed by naproxen, ibuprofen acid, diclofenac, paracetamol and aspirin. Conclusions Multicriteria decision analysis enabled participants to evaluate the OTC analgesics against a range of favourable and unfavourable effects in a group setting that enabled all issues to be openly aired and debated. The model was easily communicated and understood by the peer reviewers, so the model should be comprehensible to physicians, pharmacists and other health professionals
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