870 research outputs found

    Implementation of Time-Delay Interferometry for LISA

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    We discuss the baseline optical configuration for the Laser Interferometer Space Antenna (LISA) mission, in which the lasers are not free-running, but rather one of them is used as the main frequency reference generator (the {\it master}) and the remaining five as {\it slaves}, these being phase-locked to the master (the {\it master-slave configuration}). Under the condition that the frequency fluctuations due to the optical transponders can be made negligible with respect to the secondary LISA noise sources (mainly proof-mass and shot noises), we show that the entire space of interferometric combinations LISA can generate when operated with six independent lasers (the {\it one-way method}) can also be constructed with the {\it master-slave} system design. The corresponding hardware trade-off analysis for these two optical designs is presented, which indicates that the two sets of systems needed for implementing the {\it one-way method}, and the {\it master-slave configuration}, are essentially identical. Either operational mode could therefore be implemented without major implications on the hardware configuration. We then.......Comment: 39 pages, 6 figures, 2 table

    Effects of finite arm-length of LISA on analysis of gravitational waves from MBH binaries

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    Response of an interferometer becomes complicated for gravitational wave shorter than the arm-length of the detector, as nature of wave appears strongly. We have studied how parameter estimation for merging massive black hole binaries are affected by this complicated effect in the case of LISA. It is shown that three dimensional positions of some binaries might be determined much better than the past estimations that use the long wave approximation. For equal mass binaries this improvement is most prominent at \sim 10^5\sol.Comment: 10 pages, 3 figures, to appear in Phys.Rev.

    Cryo-EM structures of human fucosidase FucA1 reveal insight into substrate recognition and catalysis

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    Enzymatic hydrolysis of α-L-fucose from fucosylated glycoconjugates is consequential in bacterial infections and the neurodegenerative lysosomal storage disorder fucosidosis. Understanding human α-L-fucosidase catalysis, in an effort toward drug design, has been hindered by the absence of three-dimensional structural data for any animal fucosidase. Here, we have used cryoelectron microscopy (cryo-EM) to determine the structure of human lysosomal α-L-fucosidase (FucA1) in both an unliganded state and in complex with the inhibitor deoxyfuconojirimycin. These structures, determined at 2.49 Å resolution, reveal the homotetrameric structure of FucA1, the architecture of the catalytic center, and the location of both natural population variations and disease-causing mutations. Furthermore, this work has conclusively identified the hitherto contentious identity of the catalytic acid/base as aspartate-276, representing a shift from both the canonical glutamate acid/base residue and a previously proposed glutamate residue. These findings have furthered our understanding of how FucA1 functions in both health and disease.Bio-organic Synthesi

    Homogenization of weakly coupled systems of Hamilton--Jacobi equations with fast switching rates

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    We consider homogenization for weakly coupled systems of Hamilton--Jacobi equations with fast switching rates. The fast switching rate terms force the solutions converge to the same limit, which is a solution of the effective equation. We discover the appearance of the initial layers, which appear naturally when we consider the systems with different initial data and analyze them rigorously. In particular, we obtain matched asymptotic solutions of the systems and rate of convergence. We also investigate properties of the effective Hamiltonian of weakly coupled systems and show some examples which do not appear in the context of single equations.Comment: final version, to appear in Arch. Ration. Mech. Ana

    Optimal filtering of the LISA data

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    The LISA time-delay-interferometry responses to a gravitational-wave signal are rewritten in a form that accounts for the motion of the LISA constellation around the Sun; the responses are given in closed analytic forms valid for any frequency in the band accessible to LISA. We then present a complete procedure, based on the principle of maximum likelihood, to search for stellar-mass binary systems in the LISA data. We define the required optimal filters, the amplitude-maximized detection statistic (analogous to the F statistic used in pulsar searches with ground-based interferometers), and discuss the false-alarm and detection probabilities. We test the procedure in numerical simulations of gravitational-wave detection.Comment: RevTeX4, 28 pages, 9 EPS figures. Minus signs fixed in Eq. (46) and Table II. Corrected discussion of F-statistic distribution in Sec. IV

    Lichenometric dating (lichenometry) and the biology of the lichen genus rhizocarpon:challenges and future directions

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    Lichenometric dating (lichenometry) involves the use of lichen measurements to estimate the age of exposure of various substrata. Because of low radial growth rates and considerable longevity, species of the crustose lichen genus Rhizocarpon have been the most useful in lichenometry. The primary assumption of lichenometry is that colonization, growth and mortality of Rhizocarpon are similar on surfaces of known and unknown age so that the largest thalli present on the respective faces are of comparable age. This review describes the current state of knowledge regarding the biology of Rhizocarpon and considers two main questions: (1) to what extent does existing knowledge support this assumption; and (2) what further biological observations would be useful both to test its validity and to improve the accuracy of lichenometric dates? A review of the Rhizocarpon literature identified gaps in knowledge regarding early development, the growth rate/size curve, mortality, regeneration, competitive effects, colonization, and succession on rock surfaces. The data suggest that these processes may not be comparable on different rock surfaces, especially in regions where growth rates and thallus turnover are high. In addition, several variables could differ between rock surfaces and influence maximum thallus size, including rate and timing of colonization, radial growth rates, environmental differences, thallus fusion, allelopathy, thallus mortality, colonization and competition. Comparative measurements of these variables on surfaces of known and unknown age may help to determine whether the basic assumptions of lichenometry are valid. Ultimately, it may be possible to take these differences into account when interpreting estimated dates

    Global Warming: Forecasts by Scientists versus Scientific Forecasts

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    In 2007, the Intergovernmental Panel on Climate Change’s Working Group One, a panel of experts established by the World Meteorological Organization and the United Nations Environment Programme, issued its Fourth Assessment Report. The Report included predictions of dramatic increases in average world temperatures over the next 92 years and serious harm resulting from the predicted temperature increases. Using forecasting principles as our guide we asked: Are these forecasts a good basis for developing public policy? Our answer is “no”. To provide forecasts of climate change that are useful for policy-making, one would need to forecast (1) global temperature, (2) the effects of any temperature changes, and (3) the effects of feasible alternative policies. Proper forecasts of all three are necessary for rational policy making. The IPCC WG1 Report was regarded as providing the most credible long-term forecasts of global average temperatures by 31 of the 51 scientists and others involved in forecasting climate change who responded to our survey. We found no references in the 1056-page Report to the primary sources of information on forecasting methods despite the fact these are conveniently available in books, articles, and websites. We audited the forecasting processes described in Chapter 8 of the IPCC’s WG1 Report to assess the extent to which they complied with forecasting principles. We found enough information to make judgments on 89 out of a total of 140 forecasting principles. The forecasting procedures that were described violated 72 principles. Many of the violations were, by themselves, critical. The forecasts in the Report were not the outcome of scientific procedures. In effect, they were the opinions of scientists transformed by mathematics and obscured by complex writing. Research on forecasting has shown that experts’ predictions are not useful in situations involving uncertainly and complexity. We have been unable to identify any scientific forecasts of global warming. Claims that the Earth will get warmer have no more credence than saying that it will get colder

    Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic leukemia

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    Acute lymphoblastic leukemia (ALL) in infants is characterized by rearrangements of the mixed lineage leukemia (MLL) gene, drug resistance, and a poor treatment outcome. Therefore, novel therapeutic strategies are needed to improve prognosis. Recently, we showed that FLT3 is highly expressed in MLL rearranged ALL (MLL). Here we demonstrate FLT3 expression in infants with MLL (n = 41) to be significantly higher compared to both infant (n = 8; P < .001) and noninfant patients with ALL (n = 23; P = .001) carrying germline MLL genes. Furthermore, leukemic cells from infants with MLL were significantly more sensitive to the Fms-like tyrosine kinase 3 (FLT3) inhibitor PKC412 (N-benzoyl staurosporine) than noninfant ALL cells, and at least as sensitive as internal tandem duplication-positive (ITD+) AML cells. Surprisingly, activation loop mutations only occurred in about 3% (1 of 36) of the cases and no FLT3/ITDs were observed. However, measuring FLT3 phosphorylation in infants with MLL expressing varying levels of wild-type FLT3 revealed that high-level FLT3 expression is associated with ligand-independent FLT3 activation. This suggests that infant MLL cells displaying activated FLT3 as a result of overexpression can be targeted by FLT3 inhibitors such as PKC412. However, at concentrations of PKC412 minimall
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