Intratumoral Delivery of Interferon\u3b3-Secreting Mesenchymal Stromal Cells Repolarizes Tumor-Associated Macrophages and Suppresses Neuroblastoma Proliferation In Vivo

Neuroblastoma, the most common extracranial solid tumor in childhood, remains a therapeutic challenge. However, one promising patient treatment strategy is the delivery of anti-tumor therapeutic agents via mesenchymal stromal cell (MSC) therapy. MSCs have been safely used to treat genetic bone diseases such as osteogenesis imperfecta, cardiovascular diseases, autoimmune diseases, and cancer. The pro-inflammatory cytokine interferon-gamma (IFN\u3b3) has been shown to decrease tumor proliferation by altering the tumor microenvironment (TME). Despite this, clinical trials of systemic IFN\u3b3 therapy have failed due to the high blood concentration required and associated systemic toxicities. Here, we developed an intra-adrenal model of neuroblastoma, characterized by liver and lung metastases. We then engineered MSCs to deliver IFN\u3b3 directly to the TME. In vitro, these MSCs polarized murine macrophages to the M1 phenotype. In vivo, we attained a therapeutically active TME concentration of IFN\u3b3 without increased systemic concentration or toxicity. The TME-specific IFN\u3b3 reduced tumor growth rate and increased survival in two models of T cell deficient athymic nude mice. Absence of this benefit in NOD SCID gamma (NSG) immunodeficient mouse model indicates a mechanism dependent on the innate immune system. IL-17 and IL-23p19, both uniquely M1 polarization markers, transiently increased in the tumor interstitial fluid. Finally, the MSC vehicle did not promote tumor growth. These findings reveal that MSCs can deliver effective cytokine therapy directly to the tumor while avoiding systemic toxicity. This method transiently induces inflammatory M1 macrophage polarization, which reduces tumor burden in our novel neuroblastoma murine model

Spectroscopy of 24Al and extraction of Gamow-Teller strengths with the 24Mg(3He,t) reaction at 420 MeV

The 24Mg(3He,t)24Al reaction has been studied at E(3He)=420 MeV. An energy resolution of 35 keV was achieved. Gamow-Teller strengths to discrete levels in 24Al are extracted by using a recently developed empirical relationship for the proportionality between Gamow-Teller strengths and differential cross sections at zero momentum transfer. Except for small discrepancies for a few weak excitations, good agreement with previous 24Mg(p,n) data and nuclear-structure calculations using the USDA/B interactions in the sd shell-model space is found. The excitation energy of several levels in 24Al of significance for determination of the 23Mg(p,gamma)24Al thermonuclear reaction rate were measured. Results are consistent with two of the three previous (3He,t) measurements, performed at much lower beam energies. However, a new state at Ex(24Al)=2.605(10) MeV was found and is the third state above the proton separation energy.Comment: 6 pages, 4 figure

Spectroscopy of 13B via the 13C(t,3He) reaction at 115 AMeV

Gamow-Teller and dipole transitions to final states in 13B were studied via the 13C(t,3He) reaction at Et = 115 AMeV. Besides the strong Gamow-Teller transition to the 13B ground state, a weaker Gamow-Teller transition to a state at 3.6 MeV was found. This state was assigned a spin-parity of 3/2- by comparison with shell-model calculations using the WBP and WBT interactions which were modified to allow for mixing between nhw and (n+2)hw configurations. This assignment agrees with a recent result from a lifetime measurement of excited states in 13B. The shell-model calculations also explained the relatively large spectroscopic strength measured for a low-lying 1/2+ state at 4.83 MeV in 13B. The cross sections for dipole transitions up to Ex(13B)= 20 MeV excited via the 13C(t,3He) reaction were also compared with the shell-model calculations. The theoretical cross sections exceeded the data by a factor of about 1.8, which might indicate that the dipole excitations are "quenched". Uncertainties in the reaction calculations complicate that interpretation.Comment: 11 pages, 6 figure

On the extraction of weak transition strengths via the (3He,t) reaction at 420 MeV

Differential cross sections for transitions of known weak strength were measured with the (3He,t) reaction at 420 MeV on targets of 12C, 13C, 18O, 26Mg, 58Ni, 60Ni, 90Zr, 118Sn, 120Sn and 208Pb. Using this data, it is shown the proportionalities between strengths and cross sections for this probe follow simple trends as a function of mass number. These trends can be used to confidently determine Gamow-Teller strength distributions in nuclei for which the proportionality cannot be calibrated via beta-decay strengths. Although theoretical calculations in distorted-wave Born approximation overestimate the data, they allow one to understand the main experimental features and to predict deviations from the simple trends observed in some of the transitions.Comment: 4 pages, 2 figure

Beta-delayed proton emission in the 100Sn region

Beta-delayed proton emission from nuclides in the neighborhood of 100Sn was studied at the National Superconducting Cyclotron Laboratory. The nuclei were produced by fragmentation of a 120 MeV/nucleon 112Sn primary beam on a Be target. Beam purification was provided by the A1900 Fragment Separator and the Radio Frequency Fragment Separator. The fragments of interest were identified and their decay was studied with the NSCL Beta Counting System (BCS) in conjunction with the Segmented Germanium Array (SeGA). The nuclei 96Cd, 98Ing, 98Inm and 99In were identified as beta-delayed proton emitters, with branching ratios bp = 5.5(40)%, 5.5+3 -2%, 19(2)% and 0.9(4)%, respectively. The bp for 89Ru, 91,92Rh, 93Pd and 95Ag were deduced for the first time with bp = 3+1.9 -1.7%, 1.3(5)%, 1.9(1)%, 7.5(5)% and 2.5(3)%, respectively. The bp = 22(1)% for 101Sn was deduced with higher precision than previously reported. The impact of the newly measured bp values on the composition of the type-I X-ray burst ashes was studied.Comment: 15 pages, 14 Figures, 4 Table

Rethinking globalised resistance : feminist activism and critical theorising in international relations

This article argues that a feminist approach to the 'politics of resistance' offers a number of important empirical insights which, in turn, open up lines of theoretical inquiry which critical theorists in IR would do well to explore. Concretely, we draw on our ongoing research into feminist 'anti-globalisation' activism to rethink the nature of the subject of the politics of resistance, the conditions under which resistance emerges and how resistance is enacted and expressed. We begin by discussing the relationship of feminism to critical IR theory as a way of situating and explaining the focus and approach of our research project. We then summarise our key empirical arguments regarding the emergence, structure, beliefs, identities and practices of feminist 'anti-globalisation' activism before exploring the implications of these for a renewed critical theoretical agenda in IR