Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles

PEGylated gold nanoparticles are decorated with various amounts of human transferrin (Tf) to give a series of Tf-targeted particles with near-constant size and electrokinetic potential. The effects of Tf content on nanoparticle tumor targeting were investigated in mice bearing s.c. Neuro2A tumors. Quantitative biodistributions of the nanoparticles 24 h after i.v. tail-vein injections show that the nanoparticle accumulations in the tumors and other organs are independent of Tf. However, the nanoparticle localizations within a particular organ are influenced by the Tf content. In tumor tissue, the content of targeting ligands significantly influences the number of nanoparticles localized within the cancer cells. In liver tissue, high Tf content leads to small amounts of the nanoparticles residing in hepatocytes, whereas most nanoparticles remain in nonparenchymal cells. These results suggest that targeted nanoparticles can provide greater intracellular delivery of therapeutic agents to the cancer cells within solid tumors than their nontargeted analogs

Specificity of SPIO particles for characterization of liver hemangiomas using MRI

We investigated the specificity of superparamagnetic iron oxide (SPIO)â€"enhanced T1-weighted spin-echo (SE) magnetic resonance (MR) images for the characterization of liver hemangiomas. When imaging liver hemangiomas, which are the most frequent benign liver tumors, a method with very high specificity is required, which will obviate other studies, follow-up, or invasive diagnostic procedures such as percutaneous biopsy. Eighty-three lesions were examined by MR imaging at 1.5 T before and after intravenous injection of SPIO particles. Lesions were categorized as follows according to the final diagnosis: 37 hemangiomas, nine focal nodular hyperplasias (FNHs), 19 hepatocellular carcinomas (HCCs), and 18 metastases. Their signal intensity values were normalized to muscle and compared. The only lesions showing a significant increase in signal intensity ratio (lesion to muscle) on postcontrast T1-weighted SE images were hemangiomas (p < 0.001). The signal intensity ratio of hemangiomas increased on average by 70%. Based on receiver operating characteristic analysis and using a cutoff level of 50% signal increase, the specificity and sensitivity of SPIO-enhanced MR imaging for the characterization of hemangiomas would be 100% and 70%, respectively. The T1 effect of SPIO particles can help differentiate hemangiomas from other focal liver lesions such as FNHs, HCCs, and metastases and may obviate biopsy. When using SPIO particles for liver imaging, it is useful to add a T1-weighted sequence to T2-weighted images, thereby providing additional information for lesion characterizatio

The GALEX View of "Boyajian's Star" (KIC 8462852)

The enigmatic star KIC 8462852, informally known as "Boyajian's Star", has exhibited unexplained variability from both short timescale (days) dimming events, and years-long fading in the Kepler mission. No single physical mechanism has successfully explained these observations to date. Here we investigate the ultraviolet variability of KIC 8462852 on a range of timescales using data from the GALEX mission that occurred contemporaneously with the Kepler mission. The wide wavelength baseline between the Kepler and GALEX data provides a unique constraint on the nature of the variability. Using 1600 seconds of photon-counting data from four GALEX visits spread over 70 days in 2011, we find no coherent NUV variability in the system on 10-100 second or months timescales. Comparing the integrated flux from these 2011 visits to the 2012 NUV flux published in the GALEX-CAUSE Kepler survey, we find a 3% decrease in brightness for KIC 8462852. We find this level of variability is significant, but not necessarily unusual for stars of similar spectral type in the GALEX data. This decrease coincides with the secular optical fading reported by Montet & Simon (2016). We find the multi-wavelength variability is somewhat inconsistent with typical interstellar dust absorption, but instead favors a R$_V$ = 5.0 $\pm$ 0.9 reddening law potentially from circumstellar dust.Comment: 8 pages, 4 figures, ApJ Accepte

Characterizing the Cool KOIs. IV. Kepler-32 as a Prototype for the Formation of Compact Planetary Systems throughout the Galaxy

The Kepler space telescope has opened new vistas in exoplanet discovery space by revealing populations of Earth-sized planets that provide a new context for understanding planet formation. Approximately 70% of all stars in the Galaxy belong to the diminutive M dwarf class, several thousand of which lie within Kepler's field of view, and a large number of these targets show planet transit signals. The Kepler M dwarf sample has a characteristic mass of 0.5 M_☉ representing a stellar population twice as common as Sun-like stars. Kepler-32 is a typical star in this sample that presents us with a rare opportunity: five planets transit this star, giving us an expansive view of its architecture. All five planets of this compact system orbit their host star within a distance one-third the size of Mercury's orbit, with the innermost planet positioned a mere 4.3 stellar radii from the stellar photosphere. New observations limit possible false positive scenarios, allowing us to validate the entire Kepler-32 system making it the richest known system of transiting planets around an M dwarf. Based on considerations of the stellar dust sublimation radius, a minimum mass protoplanetary nebula, and the near period commensurability of three adjacent planets, we propose that the Kepler-32 planets formed at larger orbital radii and migrated inward to their present locations. The volatile content inferred for the Kepler-32 planets and order of magnitude estimates for the disk migration rates suggest that these planets may have formed beyond the snow line and migrated in the presence of a gaseous disk. If true, then this would place an upper limit on their formation time of ~10 Myr. The Kepler-32 planets are representative of the full ensemble of planet candidates orbiting the Kepler M dwarfs for which we calculate an occurrence rate of 1.0 ± 0.1 planet per star. The formation of the Kepler-32 planets therefore offers a plausible blueprint for the formation of one of the largest known populations of planets in our Galaxy

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

MOA-2016-BLG-227Lb: A Massive Planet Characterized by Combining Light-curve Analysis and Keck AO Imaging

We report the discovery of a microlensing planet—MOA-2016-BLG-227Lb—with a large planet/host mass ratio of q ≃ 9 × 10−3. This event was located near the K2 Campaign 9 field that was observed by a large number of telescopes. As a result, the event was in the microlensing survey area of a number of these telescopes, and this enabled good coverage of the planetary light-curve signal. High angular resolution adaptive optics images from the Keck telescope reveal excess flux at the position of the source above the flux of the source star, as indicated by the light-curve model. This excess flux could be due to the lens star, but it could also be due to a companion to the source or lens star, or even an unrelated star. We consider all these possibilities in a Bayesian analysis in the context of a standard Galactic model. Our analysis indicates that it is unlikely that a large fraction of the excess flux comes from the lens, unless solar-type stars are much more likely to host planets of this mass ratio than lower mass stars. We recommend that a method similar to the one developed in this paper be used for other events with high angular resolution follow-up observations when the follow-up observations are insufficient to measure the lens–source relative proper motion