Manipulation of Cellular Machinery to Produce Anti-cancer Drugs

The nocardioazine natural products are uniquely prenylated and methylated indole alkaloid diketopiperazines (DKPs) that reverse drug resistance of cancer cell lines. We unveiled the nocardioazine biosynthetic pathway from a marine actinomycete, demonstrating that a cyclodipeptide synthase catalyzes cyclo(L-Trp-L-Trp) DKP precursor formation followed by tailoring of this DKP via a novel racemase, prenyltransferase, and methyltransferase to yield nocardioazine B. These results highlight the aptitude of bacteria for chemical synthesis and offer new enzymatic tools for crafting complex organic molecules

The politics of fiscal policy during economic downturns, 1981-2010

This article investigates fiscal policy responses to the Great Recession in historical perspective. We explore general trends in the frequency, size and composition of fiscal stimulus as well as the impact of government partisanship on fiscal policy outputs during the four international recessions of 1980-81, 1990-91, 2001-02 and 2008-09. Encompassing 17-23 OECD countries, our analysis calls into question the idea of a general retreat from fiscal policy activism since the early 1980s. The propensity of governments to respond to economic downturns by engaging in fiscal stimulus has increased over time and we do not observe any secular trend in the size of stimulus measures. At the same time, OECD governments have relied more on tax cuts to stimulate demand in the two recessions of the 2000s than they did in the early 1980s or early 1990s. Regarding government partisanship, we do not find any significant direct partisan effects on either the size or the composition of fiscal stimulus for any of the four recession episodes. However, the size of the welfare state conditioned the impact of government partisanship in the two recessions of the 2000s, with Left-leaning governments distinctly more prone to engage in discretionary fiscal stimulus and/or spending increases in large welfare states, but not in small welfare states

Rapid determination of internal strains in soft tissues using an experimentally calibrated finite element model derived from magnetic resonance imaging

Background: Finite element models (FEMs) of medical images can provide information about the underlying tissue that cannot be obtained from the original images. Preforming an accurate simulation requires the careful experimental calibration of boundary conditions. Here we describe a method for deriving a geometric mesh for soft biological materials using a magnetic resonance imaging (MRI) system, and an experimental workflow for calibrating the boundary conditions and optimizing the mesh density in these simulations. Methods: A three-dimensional image stack of a ballistic sphere gel, a bovine caudal intervertebral disc (IVD), and a human lumbar IVD were generated using a positional MRI system. These images were then segmented using a semi-automated process, converted to a tetrahedral mesh, and then modeled as a linear elastic solid. The mesh density was optimized based on simulation time and convergence with the experimental results. The modulus of the ballistic gel was determined experimentally, while the material properties for the nucleus pulposus (NP) and the annulus fibrosus (AF) within the bovine and human IVDs were assigned from literature. The simulation for the spherical gel and the bovine IVD matched the reaction forces determined experimentally in compression. We then simulated a 0.3 MPa compressive load on the human lumbar IVD at the optimal mesh density and material properties determined from the bovine model and then examined the resultant internal strains. Results: The scaled mesh density demonstrated excellent correspondence with the experimental results, confirming that accuracy was not compromised. Both the ballistic gel and the IVD samples exhibited a wide range of internal strains. The NP of the IVD underwent greater deformation than the AF under loading. Conclusions: This study validated a strategy for mesh optimization and FEM of soft biological materials from data generated from MRI scans. This calibrated approach allows for the rapid examination of internal strain distributions medical images that can be performed on the order of minutes

Three-year survey of abundance, prevalence and genetic diversity of chlorovirus populations in a small urban lake

Inland water environments cover about 2.5 percent of our planet and harbor huge numbers of known and still unknown microorganisms. In this report, we examined water samples for the abundance, prevalence, and genetic diversity of a group of infectious viruses (chloroviruses) that infect symbiotic chlorella-like green algae. Samples were collected on a weekly basis for a period of 24 to 36 months from a recreational freshwater lake in Lincoln, Nebraska, and assayed for infectious viruses by plaque assay. The numbers of infectious virus particles were both host- and site-dependent. The consistent fluctuations in numbers of viruses suggest their impact as key factors in shaping microbial community structures in the water surface. Even in low-viral-abundance months, infectious chlorovirus populations were maintained, suggesting either that the viruses are very stable or that there is ongoing viral production in natural hosts. Includes supplementary figure

Wave-driven inner-shelf motions on the Oregon coast

Author Posting. © American Meteorological Society, 2009. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 39 (2009): 2942-2956, doi:10.1175/2009JPO4041.1.Recent work by S. Lentz et al. documents offshore transport in the inner shelf due to a wave-driven return flow associated with the Hasselmann wave stress (the Stokes–Coriolis force). This analysis is extended using observations from the central Oregon coast to identify the wave-driven return flow present and quantify the potential bias of wind-driven across-shelf exchange by unresolved wave-driven circulation. Using acoustic Doppler current profiler (ADCP) measurements at six stations, each in water depths of 13–15 m, observed depth-averaged, across-shelf velocities were generally correlated with theoretical estimates of the proposed return flow. During times of minimal wind forcing, across-shelf velocity profiles were vertically sheared, with stronger velocities near the top of the measured portion of the water column, and increased in magnitude with increasing significant wave height, consistent with circulation due to the Hasselmann wave stress. Yet velocity magnitudes and vertical shears were stronger than that predicted by linear wave theory, and more similar to the stratified “summer” velocity profiles described by S. Lentz et al. Additionally, substantial temporal and spatial variability of the wave-driven return flow was found, potentially due to changing wind and wave conditions as well as local bathymetric variability. Despite the wave-driven circulation found, subtracting estimates of the return flow from the observed across-shelf velocity had no significant effect on estimates of the across-shelf exchange due to along-shelf wind forcing at these water depths along the Oregon coast during summer.This work was performed with the Partnership for Interdisciplinary Studies of Coastal Oceans (PISCO), funded primarily by the Gordon and Betty Moore Foundation and David and Lucile Packard Foundation. SL acknowledges support from NSF Ocean Science Grant #OCE-0548961. AK acknowledges support from the WHOI Coastal Ocean Institute Fellowship

Multispectral thermal imaging

Many remote sensing applications rely on imaging spectrometry. Here the authors use imaging spectrometry for thermal and multispectral signatures measured from a satellite platform enhanced with a combination of accurate calibrations and on-board data for correcting atmospheric distortions. The approach is supported by physics-based end-to-end modeling and analysis, which permits a cost-effective balance between various hardware and software aspects. The goal is to develop and demonstrate advanced technologies and analysis tools toward meeting the needs of the customer; at the same time, the attributes of this system can address other applications in such areas as environmental change, agriculture, and volcanology

Spatio-temporal processes drive fine-scale genetic structure in an otherwise panmictic seabird population

When and where animals breed can shape the genetic structure and diversity of animal populations. The importance of drivers of genetic diversity is amplified in island populations that tend to have more delineated gene pools compared to continental populations. Studies of relatedness as a function of the spatial distribution of individuals have demonstrated the importance of spatial organisation for individual fitness with outcomes that are conditional on the overall genetic diversity of the population. However, few studies have investigated the impact of breeding timing on genetic structure. We characterise the fine-scale genetic structure of a geographically-isolated population of seabirds. Microsatellite markers provide evidence for largely transient within-breeding season temporal processes and limited spatial processes, affecting genetic structure in an otherwise panmictic population of sooty terns Onychoprion fuscatus. Earliest breeders had significantly different genetic structure from the latest breeders. Limited evidence was found for localised spatial structure, with a small number of individuals being more related to their nearest neighbours than the rest of the population. Therefore, population genetic structure is shaped by heterogeneities in collective movement in time and to a lesser extent space, that result in low levels of spatio-temporal genetic structure and the maintenance of genetic diversity

Low-complexity BCH codes with optimized interleavers for DQPSK systems with laser phase noise

The presence of high phase noise in addition to additive white Gaussian noise in coherent optical systems affects the performance of forward error correction (FEC) schemes. In this paper, we propose a simple scheme for such systems, using block interleavers and binary Bose–Chaudhuri–Hocquenghem (BCH) codes. The block interleavers are specifically optimized for differential quadrature phase shift keying modulation. We propose a method for selecting BCH codes that, together with the interleavers, achieve a target post-FEC bit error rate (BER). This combination of interleavers and BCH codes has very low implementation complexity. In addition, our approach is straightforward, requiring only short pre-FEC simulations to parameterize a model, based on which we select codes analytically. We aim to correct a pre-FEC BER of around (Formula presented.). We evaluate the accuracy of our approach using numerical simulations. For a target post-FEC BER of (Formula presented.), codes selected using our method result in BERs around 3(Formula presented.) target and achieve the target with around 0.2 dB extra signal-to-noise ratio

A new expression for the form stress term in the vertically Lagrangian mean framework for the effect of surface waves on the upper ocean circulation

There is an ongoing discussion in the community concerning the wave-averaged momentum equations in the hybrid vertically Lagrangian and horizontally Eulerian (VL) framework and, in particular, the form stress term (representing the residual effect of pressure perturbations) which is thought to restrict the handling of higher order waves in terms of a perturbation expansion. The present study shows that the traditional pressure-based form stress term can be transformed into a set of terms that do not contain any pressure quantities but do contain the time derivative of a wave-induced velocity. This wave-induced velocity is referred to as the pseudomomentum in the VL framework, as it is analogous to the generalized pseudomomentum in Andrews and McIntyre. This enables the second expression for the wave-averaged momentum equations in the VL framework (this time for the development of the total transport velocity minus the VL pseudomomentum) to be derived together with the vortex force. The velocity-based expression of the form stress term also contains the residual effect of the turbulent viscosity, which is useful for understanding the dissipation of wave energy leading to transfer of momentum from waves to circulation. It is found that the concept of the virtual wave stress of Longuet-Higgins is applicable to quite general situations: it does not matter whether there is wind forcing or not, the waves can have slow variations, and the viscosity coefficient can vary in the vertical. These results provide a basis for revisiting the surface boundary condition used in numerical circulation models

Crystal Structures of Tcl1 Family Oncoproteins and Their Conserved Surface Features

Members of the TCL1 family of oncogenes are abnormally expressed in mature T-cell leukemias and B-cell lymphomas. The proteins are involved in the coactivation of protein kinase B (Akt/PKB), a key intracellular kinase. The sequences and crystal structures of three Tcl1 proteins were analyzed in order to understand their interactions with Akt/PKB and the implications for lymphocyte malignancies. Tcl1 proteins are ~15 kD and share 25—80% amino acid sequence identity. The tertiary structures of mouse Tcl1, human Tcl1, and Mtcp1 are very similar. Analysis of the structures revealed conserved semi-planar surfaces that have characteristics of surfaces involved in protein-protein interactions. The Tcl1 proteins show differences in surface charge distribution and oligomeric state suggesting that they do not interact in the same way with Akt/PKB and other cellular protein(s)