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

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-γ, 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

Classification of qubit entanglement: SL(2,C) versus SU(2) invariance

The role of SU(2) invariants for the classification of multiparty entanglement is discussed and exemplified for the Kempe invariant I_5 of pure three-qubit states. It is found to being an independent invariant only in presence of both W-type entanglement and threetangle. In this case, constant I_5 admits for a wide range of both threetangle and concurrences. Furthermore, the present analysis indicates that an SL^3 orbit of states with equal tangles but continuously varying I_5 must exist. This means that I_5 provides no information on the entanglement in the system in addition to that contained in the tangles (concurrences and threetangle) themselves. Together with the numerical evidence that I_5 is an entanglement monotone this implies that SU(2) invariance or the monotone property are too weak requirements for the characterization and quantification of entanglement for systems of three qubits, and that SL(2,C) invariance is required. This conclusion can be extended to general multipartite systems (including higher local dimension) because the entanglement classes of three-qubit systems appear as subclasses.Comment: 9 pages, 10 figures, revtex

Spin Fidelity for Three-qubit Greenberger-Horne-Zeilinger and W States Under Lorentz Transformations

Constructing the reduced density matrix for a system of three massive spin$-\frac{1}{2}$ particles described by a wave packet with Gaussian momentum distribution and a spin part in the form of GHZ or W state, the fidelity for the spin part of the system is investigated from the viewpoint of moving observers in the jargon of special relativity. Using a numerical approach, it turns out that by increasing the boost speed, the spin fidelity decreases and reaches to a non-zero asymptotic value that depends on the momentum distribution and the amount of momentum entanglement.Comment: 12pages, 2 figure

Observations of the BL Lac Object 3C 66A with STACEE

We present the analysis and results of recent high-energy gamma-ray observations of the BL Lac object 3C 66A conducted with the Solar Tower Atmospheric Cherenkov Effect Experiment (STACEE). During the 2003-2004 observing season, STACEE extensively observed 3C 66A as part of a multiwavelength campaign on the source. A total of 33.7 hours of data was taken on the source, plus an equivalent-duration background observation. After cleaning the data set a total of 16.3 hours of live time remained, and a net on-source excess of 1134 events was seen against a background of 231742 events. At a significance of 2.2 standard deviations this excess is insufficient to claim a detection of 3C 66A, but is used to establish flux upper limits for the source.Comment: Accepted for publication in the Astrophysical Journa

Brownian Carnot engine

The Carnot cycle imposes a fundamental upper limit to the efficiency of a macroscopic motor operating between two thermal baths. However, this bound needs to be reinterpreted at microscopic scales, where molecular bio-motors and some artificial micro-engines operate. As described by stochastic thermodynamics, energy transfers in microscopic systems are random and thermal fluctuations induce transient decreases of entropy, allowing for possible violations of the Carnot limit. Despite its potential relevance for the development of a thermodynamics of small systems, an experimental study of microscopic Carnot engines is still lacking. Here we report on an experimental realization of a Carnot engine with a single optically trapped Brownian particle as working substance. We present an exhaustive study of the energetics of the engine and analyze the fluctuations of the finite-time efficiency, showing that the Carnot bound can be surpassed for a small number of non-equilibrium cycles. As its macroscopic counterpart, the energetics of our Carnot device exhibits basic properties that one would expect to observe in any microscopic energy transducer operating with baths at different temperatures. Our results characterize the sources of irreversibility in the engine and the statistical properties of the efficiency -an insight that could inspire novel strategies in the design of efficient nano-motors.Comment: 7 pages, 7 figure

The electric double layer has a life of its own

Using molecular dynamics simulations with recently developed importance sampling methods, we show that the differential capacitance of a model ionic liquid based double-layer capacitor exhibits an anomalous dependence on the applied electrical potential. Such behavior is qualitatively incompatible with standard mean-field theories of the electrical double layer, but is consistent with observations made in experiment. The anomalous response results from structural changes induced in the interfacial region of the ionic liquid as it develops a charge density to screen the charge induced on the electrode surface. These structural changes are strongly influenced by the out-of-plane layering of the electrolyte and are multifaceted, including an abrupt local ordering of the ions adsorbed in the plane of the electrode surface, reorientation of molecular ions, and the spontaneous exchange of ions between different layers of the electrolyte close to the electrode surface. The local ordering exhibits signatures of a first-order phase transition, which would indicate a singular charge-density transition in a macroscopic limit

Hadron Energy Reconstruction for the ATLAS Calorimetry in the Framework of the Non-parametrical Method

This paper discusses hadron energy reconstruction for the ATLAS barrel prototype combined calorimeter (consisting of a lead-liquid argon electromagnetic part and an iron-scintillator hadronic part) in the framework of the non-parametrical method. The non-parametrical method utilizes only the known $e/h$ ratios and the electron calibration constants and does not require the determination of any parameters by a minimization technique. Thus, this technique lends itself to an easy use in a first level trigger. The reconstructed mean values of the hadron energies are within $\pm 1$ of the true values and the fractional energy resolution is $[(58\pm3)/\sqrt{E}+(2.5\pm0.3)$. The value of the $e/h$ ratio obtained for the electromagnetic compartment of the combined calorimeter is $1.74\pm0.04$ and agrees with the prediction that $e/h > 1.7$ for this electromagnetic calorimeter. Results of a study of the longitudinal hadronic shower development are also presented. The data have been taken in the H8 beam line of the CERN SPS using pions of energies from 10 to 300 GeV.Comment: 33 pages, 13 figures, Will be published in NIM