468 research outputs found
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
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