Anti-Tumor Effects of TRAIL-Expressing Mesenchymal Stromal Cells in a Mouse Xenograft Model of Human Mesothelioma

Malignant mesothelioma (MM) remains a highly deadly malignancy with poor treatment option. The MM cells further promote a highly inflammatory microenvironment which contributes to tumor initiation, development, severity, and propagation. We reasoned that the anti-inflammatory actions of mesenchymal stromal cells (MSCs) and further anti-tumor effects of MSCs engineered to over-express TNF-related apoptosis inducing ligand (TRAIL) protein (MSC-TRAIL) would effectively inhibit mesothelioma growth. Using a mouse xenograft model of intraperitoneal human mesothelioma, native mouse (mMSC) or human (hMSC) MSCs were administered either systemically (IV) or intraperitoneally (IP) at various times following tumor inoculation. Both mMSCs and hMSCs localized at sites of MM tumor growth in vivo and decreased local inflammation. Further, a trend towards decrease in tumor burden was observed. Parallel studies of in vitro exposure of nine primary human mesothelioma cell lines to mMSCs or hMSCs demonstrated reduced tumor cell migration. In contrast MSC-TRAIL exposure induced apoptosis of TRAIL sensitive MM cells in vitro and both mouse and human MSC-TRAIL significantly reduced the inflammatory tumor environment in vivo. Moreover human MSC-TRAIL administration significantly reduced peritoneal tumor burden in vivo and increased tumor cell apoptosis. These proof-of-concept studies suggest that TRAIL-expressing MSCs may be useful against malignant mesothelioma

Constitutive relations, off shell duality rotations and the hypergeometric form of Born-Infeld theory

We review equivalent formulations of nonlinear and higher derivatives theories of electromagnetism exhibiting electric-magnetic duality rotations symmetry. We study in particular on shell and off shell formulations of this symmetry, at the level of action functionals as well as of equations of motion. We prove the conjecture that the action functional leading to Born-Infeld nonlinear electromagnetism, that is duality rotation invariant off shell and that is known to be a root of an algebraic equation of fourth order, is a hypergeometric function.Comment: 20 pages. Contribution to the proceedings of the conference BUDS2013, Frascat

Six-dimensional Supergravity and Projective Superfields

We propose a superspace formulation of N=(1,0) conformal supergravity in six dimensions. The corresponding superspace constraints are invariant under super-Weyl transformations generated by a real scalar parameter. The known variant Weyl super-multiplet is recovered by coupling the geometry to a super-3-form tensor multiplet. Isotwistor variables are introduced and used to define projective superfields. We formulate a locally supersymmetric and super-Weyl invariant action principle in projective superspace. Some families of dynamical supergravity-matter systems are presented.Comment: 39 pages; v3: some modifications in section 2; equations (2.3), (2.14b), (2.16) and (2.17) correcte

Extended supersymmetric sigma models in AdS_4 from projective superspace

There exist two superspace approaches to describe N=2 supersymmetric nonlinear sigma models in four-dimensional anti-de Sitter (AdS_4) space: (i) in terms of N=1 AdS chiral superfields, as developed in arXiv:1105.3111 and arXiv:1108.5290; and (ii) in terms of N=2 polar supermultiplets using the AdS projective-superspace techniques developed in arXiv:0807.3368. The virtue of the approach (i) is that it makes manifest the geometric properties of the N=2 supersymmetric sigma-models in AdS_4. The target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations on the two-sphere of complex structures. The power of the approach (ii) is that it allows us, in principle, to generate hyperkahler metrics as well as to address the problem of deformations of such metrics. Here we show how to relate the formulation (ii) to (i) by integrating out an infinite number of N=1 AdS auxiliary superfields and performing a superfield duality transformation. We also develop a novel description of the most general N=2 supersymmetric nonlinear sigma-model in AdS_4 in terms of chiral superfields on three-dimensional N=2 flat superspace without central charge. This superspace naturally originates from a conformally flat realization for the four-dimensional N=2 AdS superspace that makes use of Poincare coordinates for AdS_4. This novel formulation allows us to uncover several interesting geometric results.Comment: 88 pages; v3: typos corrected, version published in JHE

Body composition, IGF1 status, and physical functionality in nonagenarians: implications for osteosarcopenia

OBJECTIVES: Body composition alterations occur during aging. The purpose of the present analysis was to explore the functional consequences of the overlap of sarcopenia and osteoporosis, and the potential role of insulin-like growth factor 1 (IGF1) in their development in the oldest old. SETTING AND PARTICIPANTS: Eighty-seven nonagenarians from the Louisiana Healthy Aging Study were included. MEASURES: The definition of sarcopenia was based on appendicular lean mass (ALM). Osteoporosis was diagnosed based on bone mineral density (BMD) T score. Four phenotypes were compared: (1) healthy body composition, that is, nonosteoporotic nonsarcopenic (CO, control group), (2) osteoporotic (O, low BMD T score), (3) sarcopenic (S, low ALM), and (4) osteosarcopenic (OS, low BMD T score and low ALM). Sex- and age-specific IGF1-Standard Deviation Scores (SDS) were calculated. The Continuous Scale-Physical Functional Performance (CS-PFP) test was performed. RESULTS: In OS men, IGF1-SDS values (-0.61 ±0.37 vs -0.04 ± 0.52, P = .02) were lower than those in CO males (control group), whereas IGF1-SDS were similar in the 4 body composition phenotypes in women. In men only, ALM was positively associated with IGF1-SDS values (P = .01) independent of age and C-reactive protein concentration. Regarding bone health, we found no association between IGF1-SDS values and BMD. IGF1-SDS was not associated with functional performance (CS-PFP) in men and women. CONCLUSIONS/IMPLICATIONS: IGF1 sensitivity in skeletal muscle and bone may differ by sex in the oldest old. IGF1 status did not appear to affect physical functionality. Determinants and clinical and functional characteristics of osteosarcopenia need to be further investigated in order to define conclusive diagnostic criteria

Immune checkpoints in circulating and tumor-Infiltrating CD4 + T Cell Subsets in Colorectal cancer patients

Blockade of inhibitory immune checkpoints (ICs) is a promising therapeutic approach; however, it has shown limited success in some cancers including colorectal cancer (CRC). The tumor microenvironment (TME) is largely responsible for response to therapy, and its constituents may provide robust biomarkers for successful immunotherapeutic approaches. In this study, we performed phenotypical characterization and critical analyses of key inhibitory ICs and T regulatory cell (Treg)-related markers on CD4+ T cell subsets in CRC patients, and compared with normal colon tissues and peripheral blood from the same patients. We also investigated correlations between the levels of different CD4+ T cell subsets and the clinicopathologic features including disease stage and tumor budding. We found a significant increase in the levels of CD4+FoxP3+Helios+ T cells, which represent potentially highly immunosuppressive Tregs, in the CRC TME. Additionally, tumor-infiltrating CD4+ T cells upregulated programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), T cell immunoglobulin and mucin domain-3 (TIM-3) and lymphocyte-activation gene 3 (LAG-3). We also characterized the expression of PD-1, CTLA-4, TIM-3, and LAG-3 on different CD4+FoxP3−/+Helios−/+ T cell subsets. Interestingly, we found that CTLA-4, TIM-3, and LAG-3 were mainly co-expressed on FoxP3+Helios+ Tregs in the TME. Additionally, FoxP3high Tregs expressed higher levels of Helios, CTLA-4 and TIM-3 than FoxP3low T cells. These results highlight the significance of Tregs in the CRC TME and suggest that Tregs may hamper response to IC blockade in CRC patients, but effects of different IC inhibition regimes on Treg levels or activity warrants further investigations. We also found that CD4+CTLA-4+ T cells in circulation are increased in patients with advanced disease stage. This study simultaneously provides important insights into the differential levels of CD4+ T cell subpopulations and IC expression in CRC TME, compared to periphery and associations with clinicopathologic features, which could be used as potential biomarkers for CRC progression and response to therapy

Analytic pricing of contingent claims under the real-world measure

This article derives a series of analytic formulae for various contingent claims under the real-world probability measure using the stylised minimal market model (SMMM). This model provides realistic dynamics for the growth optimal portfolio (GOP) as a well-diversified equity index. It captures both leptokurtic returns with correct tail properties and the leverage effect. Under the SMMM, the discounted GOP takes the form of a time-transformed squared Bessel process of dimension four. From this property, one finds that the SMMM possesses a special and interesting relationship to non-central chi-square random variables with zero degrees of freedom. The analytic formulae derived under the SMMM include options on the GOP, options on exchange prices and options on zero-coupon bonds. For options on zero-coupon bonds, analytic prices facilitate efficient calculation of interest rate caps and floors. © 2008 World Scientific Publishing Company

Praktik Internasionalisasi Media Beritasatu Media Holdings

This study aimed to determine the practice of Internationalization carried out by BeritaSatu Media Holdings in supporting global economic interests of Lippo Group Company. Internationalization is an implication of media industrialization which the media company owner sought to reduce the spatial distance to obtain greater profits. Theory of Political Economy Media used to see how media content represents the interests of certain political economy, especially from media owners. To view the practice of Internationalization, the concept of spatialization was used. The analysis showed that the practice of Internationalization was done by BeritaSatu Media Holdings visible from nine of thirteen brand-owned media were in English, the media focused on business economics and finance or the life of the upper class, BeritaSatu Media Holdings' media distribution limited in cosmopolitan areas, some media published in Indonesia (The Straits Times, ThePeak) had editions in other countries, such as Malaysia, Singapore, and Hong Kong. Of this trend was seen that the reader of BeritaSatu Media Holdings was segmented to the expatriate community and executives. The expatriate community and executives were capital market investors and financial markets, or the part of policy makers in the field of economy both in the private and public sectors who have the power or role for the current financial turnaround either within the scope of national, regional, and multinational