Hybrid Stars in a Strong Magnetic Field

We study the effects of high magnetic fields on the particle population and equation of state of hybrid stars using an extended hadronic and quark SU(3) non-linear realization of the sigma model. In this model the degrees of freedom change naturally from hadrons to quarks as the density and/or temperature increases. The effects of high magnetic fields and anomalous magnetic moment are visible in the macroscopic properties of the star, such as mass, adiabatic index, moment of inertia, and cooling curves. Moreover, at the same time that the magnetic fields become high enough to modify those properties, they make the star anisotropic.Comment: Revised version with updated reference

Design and performance of a 35-ton liquid argon time projection chamber as a prototype for future very large detectors

Liquid argon time projection chamber technology is an attractive choice for large neutrino detectors, as it provides a high-resolution active target and it is expected to be scalable to very large masses. Consequently, it has been chosen as the technology for the first module of the DUNE far detector. However, the fiducial mass required for "far detectors" of the next generation of neutrino oscillation experiments far exceeds what has been demonstrated so far. Scaling to this larger mass, as well as the requirement for underground construction places a number of additional constraints on the design. A prototype 35-ton cryostat was built at Fermi National Acccelerator Laboratory to test the functionality of the components foreseen to be used in a very large far detector. The Phase I run, completed in early 2014, demonstrated that liquid argon could be maintained at sufficient purity in a membrane cryostat. A time projection chamber was installed for the Phase II run, which collected data in February and March of 2016. The Phase II run was a test of the modular anode plane assemblies with wrapped wires, cold readout electronics, and integrated photon detection systems. While the details of the design do not match exactly those chosen for the DUNE far detector, the 35-ton TPC prototype is a demonstration of the functionality of the basic components. Measurements are performed using the Phase II data to extract signal and noise characteristics and to align the detector components. A measurement of the electron lifetime is presented, and a novel technique for measuring a track's position based on pulse properties is described

The Modjokerto Regency Area [East Java]

Invasive fungal infections, accompanied by high rates of mortality, represent an increasing problem in medicine. Neutrophils are the major effector immune cells in fungal killing. Based on studies with neutrophils from patients with defined genetic defects, we provide evidence that human neutrophils use 2 distinct and independent phagolysosomal mechanisms to kill Candida albicans. The first mechanism for the killing of unopsonized C albicans was found to be dependent on complement receptor 3 (CR3) and the signaling proteins phosphatidylinositol-3-kinase and caspase recruitment domain-containing protein 9 (CARD9), but was independent of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The second mechanism for the killing of opsonized C albicans was strictly dependent on Fcgamma receptors, protein kinase C (PKC), and reactive oxygen species production by the NADPH oxidase system. Each of the 2 pathways of Candida killing required Syk tyrosine kinase activity, but dectin-1 was dispensable for both of them. These data provide an explanation for the variable clinical presentation of fungal infection in patients suffering from different immune defects, including dectin-1 deficiency, CARD9 deficiency, or chronic granulomatous disease

A burned-out CD8(+) T-cell subset expands in the tumor microenvironment and curbs cancer immunotherapy

Specific mechanisms by which tumor-infiltrating lymphocytes (TIL) become dysfunctional remain poorly understood. Here, we employed a two-pronged approach using single-cell mass cytometry and tissue imaging technologies to dissect TILs from 25 patients with resectable and 35 patients with advanced non-small cell lung cancer (NSCLC). We identified a burned-out CD8(+) TIL subset (Ebo) that specifically accumulated within the tumor microenvironment (TME) but not in adjacent nontumoral tissues. Ebo showed the highest expression of proliferation and activation markers but produced the lowest amount of IFN gamma and were the most apoptotic CD8(+) TIL subset. Using a humanized patient-derived tumor xenograft model, we demonstrated that Ebo expansion occurred within the TME in a PD-1/B7-H1 pathway-dependent manner. Ebo abundance in baseline tumor tissues was associated with resistance to anti-PD therapy in patients with NSCLC. Our study identifies a dysfunctional TIL subset, with distinct features from previously described exhausted T cells, and implies strategies to overcome immunotherapy resistance. SIGNIFICANCE: We identified a highly proliferative, overactivated, and apoptotic dysfunctional CD8(+) tumor-infiltrating subpopulation that is functionally distinct from previously described exhausted T cells. This population is expanded in lung cancer tissues in a PD-1/B7-H1-dependent manner, and its abundance is associated with resistance to cancer immunotherapy, thus becoming a potential tissue biomarker

A burned-out CD8(+) T-cell subset expands in the tumor microenvironment and curbs cancer immunotherapy

Specific mechanisms by which tumor-infiltrating lymphocytes (TIL) become dysfunctional remain poorly understood. Here, we employed a two-pronged approach using single-cell mass cytometry and tissue imaging technologies to dissect TILs from 25 patients with resectable and 35 patients with advanced non-small cell lung cancer (NSCLC). We identified a burned-out CD8(+) TIL subset (Ebo) that specifically accumulated within the tumor microenvironment (TME) but not in adjacent nontumoral tissues. Ebo showed the highest expression of proliferation and activation markers but produced the lowest amount of IFN gamma and were the most apoptotic CD8(+) TIL subset. Using a humanized patient-derived tumor xenograft model, we demonstrated that Ebo expansion occurred within the TME in a PD-1/B7-H1 pathway-dependent manner. Ebo abundance in baseline tumor tissues was associated with resistance to anti-PD therapy in patients with NSCLC. Our study identifies a dysfunctional TIL subset, with distinct features from previously described exhausted T cells, and implies strategies to overcome immunotherapy resistance. SIGNIFICANCE: We identified a highly proliferative, overactivated, and apoptotic dysfunctional CD8(+) tumor-infiltrating subpopulation that is functionally distinct from previously described exhausted T cells. This population is expanded in lung cancer tissues in a PD-1/B7-H1-dependent manner, and its abundance is associated with resistance to cancer immunotherapy, thus becoming a potential tissue biomarker