Identification of Myeloid Derived Suppressor Cells in Dogs with Naturally Occurring Cancer

Dogs with naturally occurring cancer represent an important large animal model for drug development and testing novel immunotherapies. However, poorly defined immunophenotypes of canine leukocytes have limited the study of tumor immunology in dogs. The accumulation of myeloid derived suppressor cells (MDSCs) is known to be a key mechanism of immune suppression in tumor-bearing mice and in human patients. We sought to identify MDSCs in the blood of dogs with cancer. Peripheral blood mononuclear cells (PBMCs) from dogs with advanced or early stage cancer and from age-matched healthy controls were analyzed by flow cytometry and microscopy. Suppressive function was tested in T cell proliferation and cytokine elaboration assays. Semi-quantitative RT-PCR was used to identify potential mechanisms responsible for immunosuppression. PBMCs from dogs with advanced or metastatic cancer exhibited a significantly higher percentage of CD11b+CD14−MHCII− cells compared to dogs diagnosed with early stage non-metastatic tumors and healthy dogs. These CD11b+ CD14−MHCII− cells constitute a subpopulation of activated granulocytes that co-purify with PBMCs, display polymorphonuclear granulocyte morphology, and demonstrate a potent ability to suppress proliferation and IFN-γ production in T cells from normal and tumor-bearing donors. Furthermore, these cells expressed hallmark suppressive factors of human MDSC including ARG1, iNOS2, TGF-β and IL-10. In summary our data demonstrate that MDSCs accumulate in the blood of dogs with advanced cancer and can be measured using this three-marker immunophenotype, thereby enabling prospective studies that can monitor MDSC burden

On a general analytical formula for U_q(su(3))-Clebsch-Gordan coefficients

We present the projection operator method in combination with the Wigner-Racah calculus of the subalgebra U_q(su(2)) for calculation of Clebsch-Gordan coefficients (CGCs) of the quantum algebra U_q(su(3)). The key formulas of the method are couplings of the tensor and projection operators and also a tensor form for the projection operator of U_q(su(3)). We obtain a very compact general analytical formula for the U_q(su(3)) CGCs in terms of the U_q(su(2)) Wigner 3nj-symbols.Comment: 9 pages, LaTeX; to be published in Yad. Fiz. (Phys. Atomic Nuclei), (2001

How Phase-Breaking Affects Quantum Transport Through Chaotic Cavities

We investigate the effects of phase-breaking events on electronic transport through ballistic chaotic cavities. We simulate phase-breaking by a fictitious lead connecting the cavity to a phase-randomizing reservoir and introduce a statistical description for the total scattering matrix, including the additional lead. For strong phase-breaking, the average and variance of the conductance are calculated analytically. Combining these results with those in the absence of phase-breaking, we propose an interpolation formula, show that it is an excellent description of random-matrix numerical calculations, and obtain good agreement with several recent experiments.Comment: 4 pages, revtex, 3 figures: uuencoded tar-compressed postscrip

Extremal projectors for contragredient Lie (super)symmetries (short review)

A brief review of the extremal projectors for contragredient Lie (super)symmetries (finite-dimensional simple Lie algebras, basic classical Lie superalgebras, infinite-dimensional affine Kac-Moody algebras and superalgebras, as well as their quantum $q$-analogs) is given. Some bibliographic comments on the applications of extremal projectors are presented.Comment: 21 pages, LaTeX; typos corrected, references adde

Ballistic Transport Through Chaotic Cavities: Can Parametric Correlations and the Weak Localization Peak be Described by a Brownian Motion Model?

A Brownian motion model is devised on the manifold of S-matrices, and applied to the calculation of conductance-conductance correlations and of the weak localization peak. The model predicts that (i) the correlation function in $B$ has the same shape and width as the weak localization peak; (ii) the functions behave as $\propto 1-{\cal O}(B^2)$, thus excluding a linear line shape; and (iii) their width increases as the square root of the number of channels in the leads. Some of these predictions agree with experiment and with other calculations only in the limit of small $B$ and a large number of channels.Comment: 5 pages revtex (twocolumn

Parametric Conductance Correlation for Irregularly Shaped Quantum Dots

We propose the autocorrelator of conductance peak heights as a signature of the underlying chaotic dynamics in quantum dots in the Coulomb blockade regime. This correlation function is directly accessible to experiments and its decay width contains interesting information about the underlying electron dynamics. Analytical results are derived in the framework of random matrix theory in the regime of broken time-reversal symmetry. The final expression, upon rescaling, becomes independent of the details of the system. For the situation when the external parameter is a variable magnetic field, the system-dependent, nonuniversal field scaling factor is obtained by a semiclassical approach. The validity of our findings is confirmed by a comparison with results of an exact numerical diagonalization of the conformal billiard threaded by a magnetic flux line.Comment: Minor corrections added to the text and references (36 pages RevTeX 3, epsf, 10 figure

Establishment and characterization of two novel patient-derived lines from canine high-grade glioma.

High-grade glioma is an aggressive cancer that occurs naturally in pet dogs. Canine high-grade glioma (cHGG) is treated with radiation, chemotherapy or surgery, but has no curative treatment. Within the past eight years, there have been advances in our imaging and histopathology standards as well as genetic charactereization of cHGG. However, there are only three cHGG cell lines publicly available, all of which were derived from astrocytoma and established using methods involving expansion of tumour cells in vitro on plastic dishes. In order to provide more clinically relevant cell lines for studying cHGG in vitro, the goal of this study was to establish cHGG patient-derived lines, whereby cancer cells are expanded in vivo by injecting cells into immunocompromized laboratory mice. The cells are then harvested from mice and used for in vitro studies. This method is the standard in the human field and has been shown to minimize the acquisition of genetic alterations and gene expression changes from the original tumour. Through a multi-institutional collaboration, we describe our methods for establishing two novel cHGG patient-derived lines, Boo-HA and Mo-HO, from a high-grade astrocytoma and a high-grade oligodendroglioma, respectively. We compare our novel lines to G06-A, J3T-Bg, and SDT-3G (traditional cHGG cell lines) in terms of proliferation and sensitivity to radiation. We also perform whole genome sequencing and identify an NF1 truncating mutation in Mo-HO. We report the characterization and availability of these novel patient-derived lines for use by the veterinary community

Signatures of Chaos in the Statistical Distribution of Conductance Peaks in Quantum Dots

Analytical expressions for the width and conductance peak distributions of irregularly shaped quantum dots in the Coulomb blockade regime are presented in the limits of conserved and broken time-reversal symmetry. The results are obtained using random matrix theory and are valid in general for any number of non-equivalent and correlated channels, assuming that the underlying classical dynamic of the electrons in the dot is chaotic or that the dot is weakly disordered. The results are expressed in terms of the channel correlation matrix which for chaotic systems is given in closed form for both point-like contacts and extended leads. We study the dependence of the distributions on the number of channels and their correlations. The theoretical distributions are in good agreement with those computed in a dynamical model of a chaotic billiard.Comment: 19 pages, RevTex, 11 Postscript figure

Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients

On September 14–15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed

Robert Nozick on nonhuman animals : rights, value and the meaning of life

In his chapter, Josh Milburn argues that Robert Nozick considers nonhuman animals in his philosophical writings, but that these discussions are downplayed in animal ethics and Nozick scholarship. This is regrettable, Milburn proposes, as Nozick is far more sympathetic to animal rights than many other libertarians. Milburn thus offers an analysis of Nozick’s animal ethics. Nozick’s arguments concerning vegetarianism and speciesism are considered, and Milburn argues that tensions in Nozick’s political philosophy potentially open the door to animal rights. Whatever their place in his political philosophy, Milburn contends, nonhuman animals find a comfortable home in Nozick’s axiology and ethics, with their value and the significance of our duties towards them affirmed. Milburn concludes that animal ethicists could learn from Nozick’s distinctive arguments and approaches and find an unexpected ally