3,088 research outputs found

    Editorial: Targeted therapies for Aggressive Cancers

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    Chemical mass transport between fluid fine tailings and the overlying water cover of an oil sands end pit lake

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    NSERC Grant No. CRDPJ 476388; NSERC Grant No. IRCPJ 428588–11Peer ReviewedFluid fine tailings (FFT) are a principal by-product of the bitumen extraction process at oil sands mines. Base Mine Lake (BML)—the first full-scale demonstration oil sands end pit lake (EPL)—contains approximately 1.9 3 108 m^3 of FFT stored under a water cover within a decommissioned mine pit. Chemical mass transfer from the FFT to the water cover can occur via two key processes: (1) advection-dispersion driven by tailings settlement; and (2) FFT disturbance due to fluid movement in the water cover. Dissolved chloride (Cl) was used to evaluate the water cover mass balance and to track mass transport within the underlying FFT based on field sampling and numerical modeling. Results indicated that FFT was the dominant Cl source to the water cover and that the FFT is exhibiting a transient advection-dispersion mass transport regime with intermittent disturbance near the FFT-water interface. The advective pore water flux was estimated by the mass balance to be 0.002 m^3 m^-2 d^-1, which represents 0.73 m of FFT settlement per year. However, the FFT pore water Cl concentrations and corresponding mass transport simulations indicated that advection rates and disturbance depths vary between sample locations. The disturbance depth was estimated to vary with location between 0.75 and 0.95 m. This investigation provides valuable insight for assessing the geochemical evolution of the water cover and performance of EPLs as an oil sands reclamation strategy

    Blood and tissue biomarker analysis in dogs with osteosarcoma treated with palliative radiation and intra-tumoral autologous natural killer cell transfer.

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    We have previously reported radiation-induced sensitization of canine osteosarcoma (OSA) to natural killer (NK) therapy, including results from a first-in-dog clinical trial. Here, we report correlative analyses of blood and tissue specimens for signals of immune activation in trial subjects. Among 10 dogs treated with palliative radiotherapy (RT) and intra-tumoral adoptive NK transfer, we performed ELISA on serum cytokines, flow cytometry for immune phenotype of PBMCs, and PCR on tumor tissue for immune-related gene expression. We then queried The Cancer Genome Atlas (TCGA) to evaluate the association of cytotoxic/immune-related gene expression with human sarcoma survival. Updated survival analysis revealed five 6-month survivors, including one dog who lived 17.9 months. Using feeder line co-culture for NK expansion, we observed maximal activation of dog NK cells on day 17-19 post isolation with near 100% expression of granzyme B and NKp46 and high cytotoxic function in the injected NK product. Among dogs on trial, we observed a trend for higher baseline serum IL-6 to predict worse lung metastasis-free and overall survival (P = 0.08). PCR analysis revealed low absolute gene expression of CD3, CD8, and NKG2D in untreated OSA. Among treated dogs, there was marked heterogeneity in the expression of immune-related genes pre- and post-treatment, but increases in CD3 and CD8 gene expression were higher among dogs that lived > 6 months compared to those who did not. Analysis of the TCGA confirmed significant differences in survival among human sarcoma patients with high and low expression of genes associated with greater immune activation and cytotoxicity (CD3e, CD8a, IFN-Îł, perforin, and CD122/IL-2 receptor beta). Updated results from a first-in-dog clinical trial of palliative RT and autologous NK cell immunotherapy for OSA illustrate the translational relevance of companion dogs for novel cancer therapies. Similar to human studies, analyses of immune markers from canine serum, PBMCs, and tumor tissue are feasible and provide insight into potential biomarkers of response and resistance

    Optimization of quantum interferometric metrological sensors in the presence of photon loss

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    We optimize two-mode entangled number states of light in the presence of loss in order to maximize the extraction of the available phase information in an interferometer. Our approach optimizes over the entire available input Hilbert space with no constraints, other than fixed total initial photon number. We optimize to maximize the Fisher information, which is equivalent to minimizing the phase uncertainty. We find that in the limit of zero loss, the optimal state is the maximally path-entangled (so-called N00N) state, for small loss, the optimal state gradually deviates from the N00N state, and in the limit of large loss, the optimal state converges to a generalized two-mode coherent state, with a finite total number of photons. The results provide a general protocol for optimizing the performance of a quantum optical interferometer in the presence of photon loss, with applications to quantum imaging, metrology, sensing, and information processing. © 2009 The American Physical Society

    Methodological Caveats in the Detection of Coordinated Replay between Place Cells and Grid Cells

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    At rest, hippocampal “place cells,” neurons with receptive fields corresponding to specific spatial locations, reactivate in a manner that reflects recently traveled trajectories. These “replay” events have been proposed as a mechanism underlying memory consolidation, or the transfer of a memory representation from the hippocampus to neocortical regions associated with the original sensory experience. Accordingly, it has been hypothesized that hippocampal replay of a particular experience should be accompanied by simultaneous reactivation of corresponding representations in the neocortex and in the entorhinal cortex, the primary interface between the hippocampus and the neocortex. Recent studies have reported that coordinated replay may occur between hippocampal place cells and medial entorhinal cortex grid cells, cells with multiple spatial receptive fields. Assessing replay in grid cells is problematic, however, as the cells exhibit regularly spaced spatial receptive fields in all environments and, therefore, coordinated replay between place cells and grid cells may be detected by chance. In the present report, we adapted analytical approaches utilized in recent studies of grid cell and place cell replay to determine the extent to which coordinated replay is spuriously detected between grid cells and place cells recorded from separate rats. For a subset of the employed analytical methods, coordinated replay was detected spuriously in a significant proportion of cases in which place cell replay events were randomly matched with grid cell firing epochs of equal duration. More rigorous replay evaluation procedures and minimum spike count requirements greatly reduced the amount of spurious findings. These results provide insights into aspects of place cell and grid cell activity during rest that contribute to false detection of coordinated replay. The results further emphasize the need for careful controls and rigorous methods when testing the hypothesis that place cells and grid cells exhibit coordinated replay

    Octopus-inspired adhesive skins for intelligent and rapidly switchable underwater adhesion

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    The octopus couples controllable adhesives with intricately embedded sensing, processing, and control to manipulate underwater objects. Current synthetic adhesive–based manipulators are typically manually operated without sensing or control and can be slow to activate and release adhesion, which limits system-level manipulation. Here, we couple switchable, octopus-inspired adhesives with embedded sensing, processing, and control for robust underwater manipulation. Adhesion strength is switched over 450× from the ON to OFF state in \u3c50 ms over many cycles with an actively controlled membrane. Systematic design of adhesive geometry enables adherence to nonideal surfaces with low preload and independent control of adhesive strength and adhesive toughness for strong and reliable attachment and easy release. Our bio-inspired nervous system detects objects and autonomously triggers the switchable adhesives. This is implemented into a wearable glove where an array of adhesives and sensors creates a biomimetic adhesive skin to manipulate diverse underwater objects

    Carbon-Enhanced Metal-Poor Stars. III. Main-Sequence Turn-Off Stars from the SDSS/SEGUE Sample

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    The chemical compositions of seven Carbon-Enhanced Metal-Poor (CEMP) turn-off stars are determined from high-resolution spectroscopy. Five of them are selected from the SDSS/SEGUE sample of metal-poor stars. The effective temperatures of these objects are all higher than 6000 K, while their metallicities, parametrized by [Fe/H], are all below -2. Six of our program objects exhibit high abundance ratios of barium ([Ba/H]> +1), suggesting large contributions of the products of former AGB companions via mass transfer across binary systems. Combining our results with previous studies provides a total of 20 CEMP main-sequence turn-off stars for which the abundances of carbon and at least some neutron-capture elements are determined. Inspection of the [C/H] ratios for this sample of CEMP turn-off stars show that they are generally higher than those of CEMP giants; their dispersion in this ratio is also smaller. We take these results to indicate that the carbon-enhanced material provided from the companion AGB star is preserved at the surface of turn-off stars with no significant dilution. In contrast, a large dispersion in the observed [Ba/H] is found for the sample of CEMP turn-off stars, suggesting that the efficiency of the s-process in very metal-poor AGB stars may differ greatly from star to star. Four of the six stars from the SDSS/SEGUE sample exhibit kinematics that are associated with membership in the outer-halo population, a remarkably high fraction.Comment: 45 pages, 10 figures, 10 tables, Astrophysical Journal, in pres

    Energy flows in vibrated granular media

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    We study vibrated granular media, investigating each of the three components of the energy flow: particle-particle dissipation, energy input at the vibrating wall, and particle-wall dissipation. Energy dissipated by interparticle collisions is well estimated by existing theories when the granular material is dilute, and these theories are extended to include rotational kinetic energy. When the granular material is dense, the observed particle-particle dissipation rate decreases to as little as 2/5 of the theoretical prediction. We observe that the rate of energy input is the weight of the granular material times an average vibration velocity times a function of the ratio of particle to vibration velocity. `Particle-wall' dissipation has been neglected in all theories up to now, but can play an important role when the granular material is dilute. The ratio between gravitational potential energy and kinetic energy can vary by as much as a factor of 3. Previous simulations and experiments have shown that E ~ V^delta, with delta=2 for dilute granular material, and delta ~ 1.5 for dense granular material. We relate this change in exponent to the departure of particle-particle dissipation from its theoretical value.Comment: 19 pages revtex, 10 embedded eps figures, accepted by PR

    Phosphorylated tau/amyloid beta 1-42 ratio in ventricular cerebrospinal fluid reflects outcome in idiopathic normal pressure hydrocephalus

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    <p>Abstract</p> <p>Background</p> <p>Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible cause of dementia and gait disturbance that is typically treated by operative placement of a ventriculoperitoneal shunt. The outcome from shunting is variable, and some evidence suggests that the presence of comorbid Alzheimer's disease (AD) may impact shunt outcome. Evidence also suggests that AD biomarkers in cerebrospinal fluid (CSF) may predict the presence of AD. The aim of this study was to investigate the relationship between the phosphorylated tau/amyloid beta 1-42 (ptau/Aβ1-42) ratio in ventricular CSF and shunt outcome in patients with iNPH.</p> <p>Methods</p> <p>We conducted a prospective trial with a cohort of 39 patients with suspected iNPH. Patients were clinically and psychometrically assessed prior to and approximately 4 months after ventriculoperitoneal shunting. Lumbar and ventricular CSF obtained intraoperatively, and tissue from intraoperative cortical biopsies were analyzed for AD biomarkers. Outcome measures included performance on clinical symptom scales, supplementary gait measures, and standard psychometric tests. We investigated relationships between the ptau/Aβ1-42 ratio in ventricular CSF and cortical AD pathology, initial clinical features, shunt outcome, and lumbar CSF ptau/Aβ1-42 ratios in the patients in our cohort.</p> <p>Results</p> <p>We found that high ptau/Aβ1-42 ratios in ventricular CSF correlated with the presence of cortical AD pathology. At baseline, iNPH patients with ratio values most suggestive of AD presented with better gait performance but poorer cognitive performance. Patients with high ptau/Aβ1-42 ratios also showed a less robust response to shunting on both gait and cognitive measures. Finally, in a subset of 18 patients who also underwent lumbar puncture, ventricular CSF ratios were significantly correlated with lumbar CSF ratios.</p> <p>Conclusions</p> <p>Levels of AD biomarkers in CSF correlate with the presence of cortical AD pathology and predict aspects of clinical presentation in iNPH. Moreover, preliminary evidence suggests that CSF biomarkers of AD may prove useful for stratifying shunt prognosis in patients being evaluated and treated for this condition.</p
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