Identification of the OGLE-2003-BLG-235/MOA-2003-BLG-53 Planetary Host Star

We present the results of HST observations of the host star for the first definitive extrasolar planet detected by microlensing. The light curve model for this event predicts that the lens star should be separated from the source star by ~6mas at the time of the HST images. If the lens star is a late G, K or early M dwarf, then it will be visible in the HST images as an additional source of light that is blended with the source image. Unless the lens and source have exactly the same colors, its presence will also be revealed by a systematic shift between centroids of the source plus lens in different filter bands. The HST data indicates both of these effects: the HST source that matches the position of the source star is 0.21 magnitudes brighter in the ACS/HRC-F814W filter than the microlensing model predicts, and there is an offset of ~0.7mas between the centroid of this source in the F814W and F435W filter bands. We conclude the planetary host star has been detected in these HST images, and this identification of the lens star enables a complete solution of the lens system. The lens parameters are determined with a Bayesian analysis, averaging over uncertainties in the measured parameters, interstellar extinction, and allowing for the possibility of a binary companion to the source star. This yields a stellar mass of M_* = 0.63(+0.07/-0.09) M_solar and a planet mass of M_p = 2.6 (+0.8/-0.6) M_Jup at an orbital separation of 4.3 (+2.5/-0.8) AU. Thus, the lens system resembles our own Solar System, with a planet of ~3 Jupiter-masses in a Jupiter-like orbit around a star of two-thirds of a Solar mass. These conclusions can be tested with future HST images, which should reveal a broadening of the blended source-plus-lens point spread function due to the relative lens-source proper motion.Comment: 11 pages, with 3 figures. to appear in ApJ Lett (Aug 20 issue

White Paper: Exoplanetary Microlensing from the Ground in the 2020s

Microlensing can access planet populations that no other method can probe: cold wide-orbit planets beyond the snow line, planets in both the Galactic bulge and disk, and free floating planets (FFPs). The demographics of each population will provide unique constraints on planet formation. Over the past 5 years, U.S. microlensing campaigns with Spitzer and UKIRT have provided a powerful complement to international ground-based microlensing surveys, with major breakthroughs in parallax measurements and probing new regions of the Galaxy. The scientific vitality of these projects has also promoted the development of the U.S. microlensing community. In the 2020s, the U.S. can continue to play a major role in ground-based microlensing by leveraging U.S. assets to complement ongoing ground-based international surveys. LSST and UKIRT microlensing surveys would probe vast regions of the Galaxy, where planets form under drastically different conditions. Moreover, while ground-based surveys will measure the planet mass-ratio function beyond the snow line, adaptive optics (AO) observations with ELTs would turn all of these mass ratios into masses and also distinguish between very wide-orbit planets and genuine FFPs. To the extent possible, cooperation of U.S. scientists with international surveys should also be encouraged and supported

Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage

20 páginas, 4 figuras, 3 tablas y 7 tablas en material suplementario.Snake venom hemorrhagic metalloproteinases (SVMPs) of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.This work was performed in partial fulfillment of the requirements for the PhD degree for Cristina Herrera at Universidad de Costa Rica.Peer reviewe

Detection of brown dwarf-like objects in the core of NGC3603

We use near-infrared data obtained with the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope to identify objects having the colors of brown dwarfs (BDs) in the field of the massive galactic cluster NGC 3603. These are identified through use of a combination of narrow and medium band filters spanning the J and H bands, and which are particularly sensitive to the presence of the 1.3-1.5{\mu}m H2O molecular band - unique to BDs. We provide a calibration of the relationship between effective temperature and color for both field stars and for BDs. This photometric method provides effective temperatures for BDs to an accuracy of {\pm}350K relative to spectroscopic techniques. This accuracy is shown to be not significantly affected by either stellar surface gravity or uncertainties in the interstellar extinction. We identify nine objects having effective temperature between 1700 and 2200 K, typical of BDs, observed J-band magnitudes in the range 19.5-21.5, and that are strongly clustered towards the luminous core of NGC 3603. However, if these are located at the distance of the cluster, they are far too luminous to be normal BDs. We argue that it is unlikely that these objects are either artifacts of our dataset, normal field BDs/M-type giants or extra-galactic contaminants and, therefore, might represent a new class of stars having the effective temperatures of BDs but with luminosities of more massive stars. We explore the interesting scenario in which these objects would be normal stars that have recently tidally ingested a Hot Jupiter, the remnants of which are providing a short-lived extended photosphere to the central star. In this case, we would expect them to show the signature of fast rotation.Comment: 26 Pages, 8 Figures, Accepted for publication on Ap

OGLE-2005-BLG-071Lb, the Most Massive M-Dwarf Planetary Companion?

We combine all available information to constrain the nature of OGLE-2005-BLG-071Lb, the second planet discovered by microlensing and the first in a high-magnification event. These include photometric and astrometric measurements from Hubble Space Telescope, as well as constraints from higher order effects extracted from the ground-based light curve, such as microlens parallax, planetary orbital motion and finite-source effects. Our primary analysis leads to the conclusion that the host of Jovian planet OGLE-2005-BLG-071Lb is an M dwarf in the foreground disk with mass M= 0.46 +/- 0.04 Msun, distance D_l = 3.3 +/- 0.4 kpc, and thick-disk kinematics v_LSR ~ 103 km/s. From the best-fit model, the planet has mass M_p = 3.8 +/- 0.4 M_Jup, lies at a projected separation r_perp = 3.6 +/- 0.2 AU from its host and so has an equilibrium temperature of T ~ 55 K, i.e., similar to Neptune. A degenerate model less favored by \Delta\chi^2 = 2.1 (or 2.2, depending on the sign of the impact parameter) gives similar planetary mass M_p = 3.4 +/- 0.4 M_Jup with a smaller projected separation, r_\perp = 2.1 +/- 0.1 AU, and higher equilibrium temperature T ~ 71 K. These results from the primary analysis suggest that OGLE-2005-BLG-071Lb is likely to be the most massive planet yet discovered that is hosted by an M dwarf. However, the formation of such high-mass planetary companions in the outer regions of M-dwarf planetary systems is predicted to be unlikely within the core-accretion scenario. There are a number of caveats to this primary analysis, which assumes (based on real but limited evidence) that the unlensed light coincident with the source is actually due to the lens, that is, the planetary host. However, these caveats could mostly be resolved by a single astrometric measurement a few years after the event.Comment: 51 pages, 12 figures, 3 tables, Published in Ap

Active PSF shaping and adaptive optics enable volumetric localization microscopy through brain sections

Application of single-molecule switching nanoscopy (SMSN) beyond the coverslip surface poses substantial challenges due to sample-induced aberrations that distort and blur single-molecule emission patterns. We combined active shaping of point spread functions and efficient adaptive optics to enable robust 3D-SMSN imaging within tissues. This development allowed us to image through 30-μm-thick brain sections to visualize and reconstruct the morphology and the nanoscale details of amyloid-β filaments in a mouse model of Alzheimer's disease

Combining the Tyrosine Kinase Inhibitor Cabozantinib and the mTORC1/2 Inhibitor Sapanisertib Blocks ERK Pathway Activity and Suppresses Tumor Growth in Renal Cell Carcinoma.

UNLABELLED: Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor regression in all models, including two from patients who experienced treatment failure with FDA-approved TKI and immunotherapy combinations. In cabozantinib-treated samples, imaging analysis revealed a significant reduction in vascular density, and single-nucleus RNA sequencing (snRNA-seq) analysis indicated a decreased proportion of endothelial cells in the tumors. SnRNA-seq data further identified a tumor subpopulation enriched with cell-cycle activity that exhibited heightened sensitivity to the cabozantinib and sapanisertib combination. Conversely, activation of the epithelial-mesenchymal transition pathway, detected at the protein level, was associated with drug resistance in residual tumors following combination treatment. The combination effectively restrained ERK phosphorylation and reduced expression of ERK downstream transcription factors and their target genes implicated in cell-cycle control and apoptosis. This study highlights the potential of the cabozantinib plus sapanisertib combination as a promising treatment approach for patients with RCC, particularly those whose tumors progressed on immune checkpoint inhibitors and other TKIs. SIGNIFICANCE: The molecular-guided therapeutic strategy of combining cabozantinib and sapanisertib restrains ERK activity to effectively suppress growth of renal cell carcinomas, including those unresponsive to immune checkpoint inhibitors