Photodynamic therapy (PDT) can lead to development of antigen-specific immune response and PDT-mediated immunity can be potentiated by T regulatory cell (Treg) depletion. We investigated whether the ...combination of PDT with cyclophosphamide (CY) could foster immunity against wild-type tumours expressing self-antigen (gp70).
Mice with CT26 tumours were treated with PDT alone or in combination with low-dose CY. T regulatory cell numbers and transforming growth factor-β (TGF-β) levels were measured at several time points after treatment. Mice cured by PDT+CY were rechallenged with CT26 and monitored for long-term survival.
Photodynamic therapy+CY led to complete tumour regression and long-term survival in 90% of treated mice while the absolute numbers of Treg decreased after PDT+CY and the TGF-β levels were reduced to a level comparable to naïve mice. Sixty-five percent of the mice treated with PDT+CY that survived over 90 days tumour free rejected the rechallenge with the same tumour when a second dose of CY was administered before rechallenge but not without.
Administration of CY before PDT led to depletion of Treg and potentiated PDT-mediated immunity, leading to long-term survival and development of memory immunity that was only uncovered by second Treg depletion.
EphA2 is a member of the Eph family of receptor tyrosine kinases and is highly expressed in many aggressive cancer types, including melanoma. We recently showed that EphA2 is also upregulated by ...ultraviolet radiation and is able to induce apoptosis. These findings suggest that EphA2 may have different, even paradoxical, effects on viability depending on the cellular context and that EphA2 mediates a delicate balance between life and death of the cell. To functionally clarify EphA2's role in melanoma, we analyzed a panel of melanoma cell lines and found that EphA2 levels are elevated in a significant fraction of the samples. Specific depletion of EphA2 in high-expressing melanoma cells using short hairpin RNA led to profound reductions in cellular viability, colony formation and migration in vitro and a dramatic loss of tumorigenic potential in vivo. Stable introduction of EphA2 into low-expressing cell lines enhanced proliferation, colony formation and migration, further supporting its pro-malignant phenotype. Interestingly, transient expression of EphA2 and/or Braf(V600E) in non-transformed melanocytes led to significant and additive apoptosis. These results verify that EphA2 is an important oncogene and potentially a common source of 'addiction' for many melanoma cells. Moreover, acute induction of EphA2 may purge genetically susceptible cells, thereby uncovering a more aggressive population that is in fact dependent on the oncogene.
We present the analysis of the simultaneous high-resolution images from the Hubble Space Telescope and Keck adaptive optics system of the planetary event OGLE-2012-BLG-0950 that determine that the ...system consists of a 0.58 0.04 host star orbited by a 39 8 planet at a projected separation of 2.54 0.23 au. The planetary system is located at a distance of 2.19 0.23 kpc from Earth. This is the second microlens planet beyond the snow line with a mass measured to be in the mass range 20-80 . The runaway gas accretion process of the core accretion model predicts fewer planets in this mass range. This is because giant planets are thought to be growing rapidly at these masses, and they rarely complete growth at this mass. So this result suggests that the core accretion theory may need revision. This analysis also demonstrates the techniques that will be used to measure the masses of planets and their host stars by the WFIRST exoplanet microlensing survey: one-dimensional microlensing parallax combined with the separation and brightness measurement of the unresolved source and host stars to yield multiple redundant constraints on the masses and distance of the planetary system.
Most stellar remnants so far have been found in binary systems, where they interact with matter from their companions. Isolated neutron stars and black holes are difficult to find as they are dark, ...yet they are predicted to exist in our Galaxy in vast numbers. We explored the OGLE-III data base of 150 million objects observed in years 2001–2009 and found 59 microlensing events exhibiting a parallax effect due to the Earth's motion around the Sun. Combining parallax and brightness measurements from microlensing light curves with expected proper motions in the Milky Way, we identified 13 microlensing events which are consistent with having a white dwarf, neutron star or a black hole lens and we estimated their masses and distances. The most massive of our black hole candidates has 9.3 M⊙ and is at a distance of 2.4 kpc. The distribution of masses of our candidates indicates a continuum in mass distribution with no mass gap between neutron stars and black holes. We also present predictions on how such events will be observed by the astrometric Gaia mission.
We present the most extensive and detailed reddening maps of the Magellanic Clouds (MCs) derived from the color properties of Red Clump (RC) stars. The analysis is based on the deep photometric maps ...from the fourth phase of the Optical Gravitational Lensing Experiment (OGLE-IV), covering approximately 670 deg2 of the sky in the Magellanic System region. The resulting maps provide reddening information for 180 deg2 in the Large Magellanic Cloud (LMC) and 75 deg2 in the Small Magellanic Cloud (SMC), with a resolution of 1 7 × 1 7 in the central parts of the MCs, decreasing to approximately 27′ × 27′ in the outskirts. The mean reddening is E(V − I) = 0.100 0.043 mag in the LMC and E(V − I) = 0.047 0.025 mag in the SMC. We refine methods of calculating the RC color to obtain the highest possible accuracy of reddening maps based on RC stars. Using spectroscopy of red giants, we find the metallicity gradient in both MCs, which causes a slight decrease of the intrinsic RC color with distance from the galaxy center of ∼0.002 mag/deg in the LMC and between 0.003 and 0.009 mag/deg in the SMC. The central values of the intrinsic RC color are 0.886 and 0.877 mag in the LMC and SMC, respectively. The reddening map of the MCs is available both in downloadable form and as an interactive interface.
Abstract Dendritic cells (DC) play a role in the regulation of immune responses to haptens, which in turn impact DC maturation. Whether beryllium (Be) is able to induce DC maturation and if this ...occurs via the MAPK pathway is not known. Primary monocyte-derived DCs (moDCs) models were generated from Be non-exposed healthy volunteers as a non-sensitized cell model, while PBMCs from BeS (Be sensitized) and CBD (chronic beryllium disease) were used as disease models. The response of these cells to Be was evaluated. The expression of CD40 was increased significantly ( p < 0.05) on HLA-DP Glu69+ moDCs after 100 μM BeSO4 -stimulation. BeSO4 induced p38MAPK phosphorylation, while IκB-α was degraded in Be-stimulated moDCs. The p38 MAPK inhibitor SB203580 blocked Be-induced NF-κB activation in moDCs, suggesting that p38MAPK and NF-κB are dependently activated by BeSO4 . Furthermore, in BeS and CBD subjects, SB203580 downregulated Be-stimulated proliferation in a dose-dependent manner, and decreased Be-stimulated TNF-α and IFNγ cytokine production. Taken together, this study suggests that Be-induces non-sensitized Glu69+ DCs maturation, and that p38MAPK signaling is important in the Be-stimulated DCs activation as well as subsequent T cell proliferation and cytokine production in BeS and CBD. In total, the MAPK pathway may serve as a potential therapeutic target for human granulomatous lung diseases.
Abstract We report the discovery of the classical Cepheid OGLE-GD-CEP-1884 (= GDS_J1535467-555656) with the longest pulsation period known in our Galaxy. The period of 78.14 days is nearly 10 days ...longer than that of the previous record-holding Cepheid, S Vulpeculae, and thus, OGLE-GD-CEP-1884 can be categorized as the first ultra-long-period Cepheid in the Milky Way. This star is present in the ASAS-SN and Gaia DR3 catalogs of variable stars, but it has been classified as a long-period variable in those catalogs. Based on more than 10 yr of the photometric monitoring of this star carried out by the OGLE project in the I and V bands and a radial velocity curve from the Gaia Focused Product Release, we unequivocally demonstrate that this object is a fundamental-mode classical Cepheid. By employing the mid-infrared period–luminosity relation, we determine the distance to OGLE-GD-CEP-1884 (4.47 ± 0.34 kpc) and place it on the Milky Way map, along with about 2400 other classical Cepheids. We also discuss the potential of finding additional ultra-long-period Cepheids in our Galaxy.
This longitudinal study explores how the language proficiency of eight (N = 8) US‐affiliated university students developed relative to their smartphone usage during study abroad (SA) in Paris. Phone ...usage was tracked daily with Space, proficiency weekly using NCSSFL‐ACTFL Can‐Do statements, and language use monthly via a Language Engagement Questionnaire. Adopting a Complex Dynamic Systems Theory (CDST) framework and following a microgenetic approach to case studies, the trajectories of each participant's phone consumption and Can‐Do statements were established, allowing to visualize floors, ceilings, and probes in proficiency development. Spearman's correlations served to determine whether and how phone usage related to fluctuations in proficiency, and Kendall's tau‐b its link with language used. Findings revealed that these relationships varied widely across participants, types of phone usage, and phone applications, with students displaying positive, mixed, or negative relationships, thus suggesting that there is no one‐size‐fits‐all model to proficiency/smartphone management, but idiosyncratic complex cases.
The Challenge
Because they allow to maintain a constant connection with home, smartphones have been assumed to negatively impact the linguistic development of students abroad. Yet, this claim warrants further scrutiny. Are smartphones used during study abroad friends or foes? This study documents the relationship between smartphone usage and proficiency development.
PDF
