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We present results from three world-wide campaigns that resulted in the detections of two single-chord and one multi-chord stellar occultations by the Plutino object (84922) 2003~VS\\(_2\\). From the single-chord occultations in 2013 and 2014 we obtained accurate astrometric positions for the object, while from the multi-chord occultation on November 7th, 2014, we obtained the parameters of the best-fitting ellipse to the limb of the body at the time of occultation. We also obtained short-term photometry data for the body in order to derive its rotational phase during the occultation. The rotational light curve present a peak-to-peak amplitude of 0.141 \\(\\pm\\) 0.009 mag. This allows us to reconstruct the three-dimensional shape of the body, with principal semi-axes \\(a = 313.8 \\pm 7.1\\) km, \\(b = 265.5^{+8.8}_{-9.8}\\) km, and \\(c = 247.3^{+26.6}_{-43.6}\\) km, which is not consistent with a Jacobi triaxial equilibrium figure. The derived spherical volume equivalent diameter of \\(548.3 ^{+29.5}_{-44.6}\\) km is about 5\\% larger than the radiometric diameter of 2003~VS\\(_2\\) derived from Herschel data of \\(523 \\pm 35\\) km, but still compatible with it within error bars. From those results we can also derive the geometric albedo (\\(0.123 ^{+0.015}_{-0.014}\\)) and, under the assumption that the object is a Maclaurin spheroid, the density \\(\\rho = 1400^{+1000}_{-300}\\) for the plutino. The disappearances and reappearances of the star during the occultations do not show any compelling evidence for a global atmosphere considering a pressure upper limit of about 1 microbar for a pure nitrogen atmosphere, nor secondary features (e.g. rings or satellite) around the main body.

Context. The so-called Barbarian asteroids share peculiar, but common polarimetric properties, probably related to both their shape and composition. They are named after (234) Barbara, the first on which such properties were identified. As has been suggested, large scale topographic features could play a role in the polarimetric response, if the shapes of Barbarians are particularly irregular and present a variety of scattering/incidence angles. This idea is supported by the shape of (234) Barbara, that appears to be deeply excavated by wide concave areas revealed by photometry and stellar occultations. Aims. With these motivations, we started an observation campaign to characterise the shape and rotation properties of Small Main- Belt Asteroid Spectroscopic Survey (SMASS) type L and Ld asteroids. As many of them show long rotation periods, we activated a worldwide network of observers to obtain a dense temporal coverage. Methods. We used light-curve inversion technique in order to determine the sidereal rotation periods of 15 asteroids and the con- vergence to a stable shape and pole coordinates for 8 of them. By using available data from occultations, we are able to scale some shapes to an absolute size. We also study the rotation periods of our sample looking for confirmation of the suspected abundance of asteroids with long rotation periods. Results. Our results show that the shape models of our sample do not seem to have peculiar properties with respect to asteroids with similar size, while an excess of slow rotators is most probably confirmed.

The Centaur (10199) Chariklo has the first rings system discovered around a small object. It was first observed using stellar occultation in 2013. Stellar occultations allow the determination of sizes and shapes with kilometre accuracy and obtain characteristics of the occulting object and its vicinity. Using stellar occultations observed between 2017 and 2020, we aim at constraining Chariklo's and its rings physical parameters. We also determine the rings' structure, and obtain precise astrometrical positions of Chariklo. We predicted and organised several observational campaigns of stellar occultations by Chariklo. Occultation light curves were measured from the data sets, from which ingress and egress times, and rings' width and opacity were obtained. These measurements, combined with results from previous works, allow us to obtain significant constraints on Chariklo's shape and rings' structure. We characterise Chariklo's ring system (C1R and C2R), and obtain radii and pole orientations that are consistent with, but more accurate than, results from previous occultations. We confirmed the detection of W-shaped structures within C1R and an evident variation of radial width. The observed width ranges between 4.8 and 9.1 km with a mean value of 6.5 km. One dual observation (visible and red) does not reveal any differences in the C1R opacity profiles, indicating ring particle's size larger than a few microns. The C1R ring eccentricity is found to be smaller than 0.022 (3-sigma), and its width variations may indicate an eccentricity higher than 0.005. We fit a tri-axial shape to Chariklo's detections over eleven occultations and determine that Chariklo is consistent with an ellipsoid with semi-axes of 143.8, 135.2 and 99.1 km. Ultimately, we provided seven astrometric positions at a milliarcseconds accuracy level, based on Gaia EDR3, and use it to improve Chariklo's ephemeris.

Peptides and biologics provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. Most peptides and biologics are fused with cationic uptake moieties or formulated into nanoparticles to facilitate delivery, but these systems typically lack potency due to low uptake and/or entrapment and degradation in endolysosomal compartments. Because most delivery reagents comprise cationic lipids or polymers, there is a lack of reagents specifically optimized to deliver cationic cargo. Herein, we demonstrate the utility of the cytocompatible polymer poly(propylacrylic acid) (PPAA) to potentiate intracellular delivery of cationic biomacromolecules and nano-formulations. This approach demonstrates superior efficacy over all marketed peptide delivery reagents and enhances delivery of nucleic acids and gene editing ribonucleoproteins (RNPs) formulated with both commercially-available and our own custom-synthesized cationic polymer delivery reagents. These results demonstrate the broad potential of PPAA to serve as a platform reagent for the intracellular delivery of cationic cargo. Most reagents designed to deliver cargo into cells are cationic and so cannot deliver cationic cargo. Here the authors show that pretreating cells with the anionic polymer poly(propylacrylic acid) facilitates the uptake and endosomal escape of a wide variety of cationic cargo in numerous cell types.

The high potential of siRNAs to silence oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, divalent lipid-conjugated siRNAs are optimized for in situ binding to albumin to improve pharmacokinetics and tumor delivery. Systematic variation of the siRNA conjugate structure reveals that the location of the linker branching site dictates tendency toward albumin association versus self-assembly, while the lipid hydrophobicity and reversibility of albumin binding also contribute to siRNA intracellular delivery. The lead structure increases tumor siRNA accumulation 12-fold in orthotopic triple negative breast cancer (TNBC) tumors over the parent siRNA. This structure achieves approximately 80% silencing of the anti-apoptotic oncogene MCL1 and yields better survival outcomes in three TNBC models than an MCL-1 small molecule inhibitor. These studies provide new structure-function insights on siRNA-lipid conjugate structures that are intravenously injected, associate in situ with serum albumin, and improve pharmacokinetics and tumor treatment efficacy. Limited tumor cell delivery is a major challenge for the efficacious delivery of siRNAs to silence traditionally undruggable oncogenes. Here the authors optimize siRNAs for in situ binding to albumin through C18 lipid modifications and show the application of the lead conjugate structure for targeting MCL1 in orthotopic breast tumors in mice.

BackgroundGiven the complex three-dimensional (3D) anatomy of head and neck cancer specimens, head and neck surgeons often have difficulty relocating the site of an initial positive margin to perform re-resection. This cadaveric study aimed to determine the feasibility and accuracy of augmented reality surgery to guide head and neck cancer re-resections.MethodsThis study investigated three cadaveric specimens. The head and neck resection specimen was 3D scanned and exported to the HoloLens augmented reality environment. The surgeon manually aligned the 3D specimen hologram into the resection bed. Accuracy of manual alignment and time intervals throughout the protocol were recorded.ResultsThe 20 head and neck cancer resections performed in this study included 13 cutaneous and 7 oral cavity resections. The mean relocation error was 4 mm (range, 1–15 mm) with a standard deviation of 3.9 mm. The mean overall protocol time, from the start of 3D scanning to alignment into the resection bed, was 25.3 ± 8.9 min (range, 13.2–43.2 min). Relocation error did not differ significantly when stratified by greatest dimension of the specimen. The mean relocation error of complex oral cavity composite specimens (maxillectomy and mandibulectomy) differed significantly from that of all the other specimen types (10.7 vs 2.8; p < 0.01).ConclusionsThis cadaveric study demonstrated the feasibility and accuracy of augmented reality to guide re-resection of initial positive margins in head and neck cancer surgery.

Background Surgical resection is the primary treatment for bone and soft tissue tumors. Negative margin status is a key factor in prognosis. Given the three-dimensional (3D) anatomic complexity of musculoskeletal tumor specimens, communication of margin results between surgeons and pathologists is challenging. We sought to perform ex vivo 3D scanning of musculoskeletal oncology specimens to enhance communication between surgeons and pathologists. Methods Immediately after surgical resection, 3D scanning of the fresh specimen is performed prior to frozen section analysis. During pathologic grossing, whether frozen or permanent, margin sampling sites are annotated on the virtual 3D model using computer-aided design (CAD) software. Results 3D scanning was performed in seven cases (six soft tissue, one bone), with specimen mapping on six cases. Intraoperative 3D scanning and mapping was performed in one case in which the location of margin sampling was shown virtually in real-time to the operating surgeon to help achieve a negative margin. In six cases, the 3D model was used to communicate final permanent section analysis. Soft tissue, cartilage, and bone (including lytic lesions within bone) showed acceptable resolution. Conclusions Virtual 3D scanning and specimen mapping is feasible and may allow for enhanced documentation and communication. This protocol provides useful information for anatomically complex musculoskeletal tumor specimens. Future studies will evaluate the effect of the protocol on positive margin rates, likelihood that a re-resection contains additional malignancy, and exploration of targeted adjuvant radiation protocols using a patient-specific 3D specimen map.