873 research outputs found
Possible strong symmetric hydrogen bonding in disodium trihydrogen bis(2,2'-oxydiacetate) nitrate
In the title compound, 2Na+·C8H11O10-·NO3-, the NaI atom is heptacoordinate with an approximately pentagonal-bipyramidal geometry. A possible strong symmetric hydrogen bond, with the H atom located at an inversion centre and an OO distance of 2.450 (2) Å, is observed in the crystal structure
T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression.
Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of protumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)-bearing T cells to recognize human prostate-specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA(+) endothelial targets in vitro, regardless of the signaling domain. T cells bearing the third-generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA(+) vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide a strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. Cancer Immunol Res; 3(1); 68-84. ©2014 AACR
Spin Fluctuations and the Magnetic Phase Diagram of ZrZn2
The magnetic properties of the weak itinerant ferromagnet ZrZn_2 are analyzed
using Landau theory based on a comparison of density functional calculations
and experimental data as a function of field and pressure. We find that the
magnetic properties are strongly affected by the nearby quantum critical point,
even at zero pressure; LDA calculations neglecting quantum critical spin
fluctuations overestimate the magnetization by a factor of approximately three.
Using renormalized Landau theory, we extract pressure dependence of the
fluctuation amplitude. It appears that a simple scaling based on the
fluctuation-dissipation theorem provides a good description of this pressure
dependence.Comment: 4 revtex page
Parallelization of the discrete gradient method of non-smooth optimization and its applications
We investigate parallelization and performance of the discrete gradient method of nonsmooth optimization. This derivative free method is shown to be an effective optimization tool, able to skip many shallow local minima of nonconvex nondifferentiable objective functions. Although this is a sequential iterative method, we were able to parallelize critical steps of the algorithm, and this lead to a significant improvement in performance on multiprocessor computer clusters. We applied this method to a difficult polyatomic clusters problem in computational chemistry, and found this method to outperform other algorithms. <br /
Ab-initio study of BaTiO3 surfaces
We have carried out first-principles total-energy calculations of (001)
surfaces of the tetragonal and cubic phases of BaTiO3. Both BaO-terminated
(type I) and TiO2-terminated (type II) surfaces are considered, and the atomic
configurations have been fully relaxed. We found no deep-gap surface states for
any of the surfaces, in agreement with previous theoretical studies. However,
the gap is reduced for the type-II surface, especially in the cubic phase. The
surface relaxation energies are found to be substantial, i.e., many times
larger than the bulk ferroelectric well depth. Nevertheless, the influence of
the surface upon the ferroelectric order parameter is modest; we find only a
small enhancement of the ferroelectricity near the surface.Comment: 8 pages, two-column style with 4 postscript figures embedded. Uses
REVTEX and epsf macros. Also available at
http://www.physics.rutgers.edu/~dhv/preprints/index.html#pad_sur
An oncogenic role for sphingosine kinase 2
While both human sphingosine kinases (SK1 and SK2) catalyze the generation of the pleiotropic signaling lipid sphingosine 1-phosphate, these enzymes appear to be functionally distinct. SK1 has well described roles in promoting cell survival, proliferation and neoplastic transformation. The roles of SK2, and its contribution to cancer, however, are much less clear. Some studies have suggested an antiproliferative/ pro-apoptotic function for SK2, while others indicate it has a prosurvival role and its inhibition can have anti-cancer effects. Our analysis of gene expression data revealed that SK2 is upregulated in many human cancers, but only to a small extent (up to 2.5-fold over normal tissue). Based on these findings, we examined the effect of different levels of cellular SK2 and showed that high-level overexpression reduced cell proliferation and survival, and increased cellular ceramide levels. In contrast, however, low-level SK2 overexpression promoted cell survival and proliferation, and induced neoplastic transformation in vivo. These findings coincided with decreased nuclear localization and increased plasma membrane localization of SK2, as well as increases in extracellular S1P formation. Hence, we have shown for the first time that SK2 can have a direct role in promoting oncogenesis, supporting the use of SK2-specific inhibitors as anti-cancer agents.Heidi A. Neubauer, Duyen H. Pham, Julia R. Zebol, Paul A.B. Moretti, Amanda L. Peterson, Tamara M. Leclercq, Huasheng Chan, Jason A. Powell, Melissa R. Pitman, Michael S. Samuel, Claudine S. Bonder, Darren J. Creek, Briony L. Gliddon and Stuart M. Pitso
An Experimental Investigation of Colonel Blotto Games
"This article examines behavior in the two-player, constant-sum Colonel Blotto game with asymmetric resources in which players maximize the expected number of battlefields won. The experimental results support all major theoretical predictions. In the auction treatment, where winning a battlefield is deterministic, disadvantaged players use a 'guerilla warfare' strategy which stochastically allocates zero resources to a subset of battlefields. Advantaged players employ a 'stochastic complete coverage' strategy, allocating random, but positive, resource levels across the battlefields. In the lottery treatment, where winning a battlefield is probabilistic, both players divide their resources equally across all battlefields." (author's abstract)"Dieser Artikel untersucht das Verhalten von Individuen in einem 'constant-sum Colonel Blotto'-Spiel zwischen zwei Spielern, bei dem die Spieler mit unterschiedlichen Ressourcen ausgestattet sind und die erwartete Anzahl gewonnener Schlachtfelder maximieren. Die experimentellen Ergebnisse bestätigen alle wichtigen theoretischen Vorhersagen. Im Durchgang, in dem wie in einer Auktion der Sieg in einem Schlachtfeld deterministisch ist, wenden die Spieler, die sich im Nachteil befinden, eine 'Guerillataktik' an, und verteilen ihre Ressourcen stochastisch auf eine Teilmenge der Schlachtfelder. Spieler mit einem Vorteil verwenden eine Strategie der 'stochastischen vollständigen Abdeckung', indem sie zufällig eine positive Ressourcenmenge auf allen Schlachtfeldern positionieren. Im Durchgang, in dem sich der Gewinn eines Schlachtfeldes probabilistisch wie in einer Lotterie bestimmt, teilen beide Spieler ihre Ressourcen gleichmäßig auf alle Schlachtfelder auf." (Autorenreferat
Finite element simulation of three-dimensional free-surface flow problems
An adaptive finite element algorithm is described for the stable solution of three-dimensional free-surface-flow problems based primarily on the use of node movement. The algorithm also includes a discrete remeshing procedure which enhances its accuracy and robustness. The spatial discretisation allows an isoparametric piecewise-quadratic approximation of the domain geometry for accurate resolution of the curved free surface.
The technique is illustrated through an implementation for surface-tension-dominated viscous flows modelled in terms of the Stokes equations with suitable boundary conditions on the deforming free surface. Two three-dimensional test problems are used to demonstrate the performance of the method: a liquid bridge problem and the formation of a fluid droplet
Single-field inflation constraints from CMB and SDSS data
We present constraints on canonical single-field inflation derived from WMAP
five year, ACBAR, QUAD, BICEP data combined with the halo power spectrum from
SDSS LRG7. Models with a non-scale-invariant spectrum and a red tilt n_s < 1
are now preferred over the Harrison-Zel'dovich model (n_s = 1, tensor-to-scalar
ratio r = 0) at high significance. Assuming no running of the spectral indices,
we derive constraints on the parameters (n_s, r) and compare our results with
the predictions of simple inflationary models. The marginalised credible
intervals read n_s = 0.962^{+0.028}_{-0.026} and r < 0.17 (at 95% confidence
level). Interestingly, the 68% c.l. contours favour mainly models with a convex
potential in the observable region, but the quadratic potential model remains
inside the 95% c.l. contours. We demonstrate that these results are robust to
changes in the datasets considered and in the theoretical assumptions made. We
then consider a non-vanishing running of the spectral indices by employing
different methods, non-parametric but approximate, or parametric but exact.
With our combination of CMB and LSS data, running models are preferred over
power-law models only by a Delta chi^2 ~ 5.8, allowing inflationary stages
producing a sizable negative running -0.063^{+0.061}_{-0.049} and larger
tensor-scalar ratio r < 0.33 at the 95% c.l. This requires large values of the
third derivative of the inflaton potential within the observable range. We
derive bounds on this derivative under the assumption that the inflaton
potential can be approximated as a third order polynomial within the observable
range.Comment: 32 pages, 7 figures. v2: additional references, some typos corrected,
passed to JCAP style. v3: minor changes, matches published versio
The Ovarian Cancer Chemokine Landscape Is Conducive to Homing of Vaccine-Primed and CD3/CD28-Costimulated T Cells Prepared for Adoptive Therapy.
PURPOSE: Chemokines are implicated in T-cell trafficking. We mapped the chemokine landscape in advanced stage ovarian cancer and characterized the expression of cognate receptors in autologous dendritic cell (DC)-vaccine primed T cells in the context of cell-based immunotherapy.
EXPERIMENTAL DESIGN: The expression of all known human chemokines in patients with primary ovarian cancer was analyzed on two independent microarray datasets and validated on tissue microarray. Peripheral blood T cells from five HLA-A2 patients with recurrent ovarian cancer, who previously received autologous tumor DC vaccine, underwent CD3/CD28 costimulation and expansion ex vivo. Tumor-specific T cells were identified by HER2/neu pentamer staining and were evaluated for the expression and functionality of chemokine receptors important for homing to ovarian cancer.
RESULTS: The chemokine landscape of ovarian cancer is heterogeneous with high expression of known lymphocyte-recruiting chemokines (CCL2, CCL4, and CCL5) in tumors with intraepithelial T cells, whereas CXCL10, CXCL12, and CXCL16 are expressed quasi-universally, including in tumors lacking tumor-infiltrating T cells. DC-vaccine primed T cells were found to express the cognate receptors for the above chemokines. Ex vivo CD3/CD28 costimulation and expansion of vaccine-primed Tcells upregulated CXCR3 and CXCR4, and enhanced their migration toward universally expressed chemokines in ovarian cancer.
CONCLUSIONS: DC-primed tumor-specific T cells are armed with the appropriate receptors to migrate toward universal ovarian cancer chemokines, and these receptors are further upregulated by ex vivo CD3/CD28 costimulation, which render T cells more fit for migrating toward these chemokines. Clin Cancer Res; 21(12); 2840-50. ©2015 AACR
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