The Near-Earth Encounter of Asteroid 308635 (2005 YU55): Thermal IR Observations

The near-Earth approach (0.00217 AU, or 0.845 lunar distances) of the C-type asteroid 308635 (2005 YU55) in November 2011 presented a rare opportunity for detailed observations of a low-albedo NEA in this size range. As part of a multi-telescope campaign to measure visible and infrared spectra and photometry, we obtained mid-infrared (approx. 8 to 22 micron) photometry and spectroscopy of 2005 YU55 using Michelle on the Gemini North telescope on UT November 9 and 10,2011. An extensive radar campaign together with optical light-curves established the rotation state of YU55. In addition, the radar imaging resulted in a shape model for the asteroid, detection of numerous boulders on its surface, and a preliminary estimate of its equatorial diameter at 380 +/- 20 m. In a preliminary analysis, applying the radar and lightcurve-derived parameters to a rough-surface thermophysical model fit to the Gemini/Michelle thermal emission photometry results in a thermal inertia range of approximately 500 to 1500 J/sq m/0.5s/K, with the low-thermal-inertia solution corresponding to the small end of the radar size range and vice versa. Updates to these results will be presented and modeling of the thermal contribution to the measured near-infrared spectra from Palomar/Triplespec and IRTF/SpeX will also be discussed

Circulating miRNA Biomarkers in Early Breast Cancer Detection following Mammography

The currently accepted stepwise model of breast tumorigenesis assumes a gradual transition from normal breast epithelial cells to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS) and then to invasive ductal carcinoma (IDC). Percutaneous core needle biopsy (CNB) is the standard technique following an abnormal mammographic finding. However, CNB is less reliable in differentiating simple ADH (sADH) from ADH component coexisted with advanced lesions such as DCIS and/or IDC (cADH). Therefore, to identify and validate novel reliable molecular biomarkers is essential in order to improve the efficiency of therapeutic recommendations, as well as to minimize anxiety and unnecessary procedures. miRNAs function as tumor suppressors or oncogenes and play a critical role in cancer initiation and progression by regulating their target genes. Unlike messenger RNAs (mRNAs), which could be easily degraded, miRNAs are found to be stable not only in body fluid, but also in Formalin-Fixed, Paraffin-Embedded (FFPE) tissues. The stability of miRNAs in FFPE and blood samples suggests that they may be the ideal biomarkers for the early diagnosis and prognosis of cancer, including breast cancer. The goal of this research is to use FFPE and blood samples from the two different groups of patients, analyze the candidate miRNAs to differentiating simple sADH from cADH. In our published studies, we identified a series of miRNAs that are differentially expressed during stepwise transition of breast carcinogenesis, including miR-671-5p. In this study, we showed that the expression of miR-671-5p and miR-638 decreases in ADH, DCIS, and IDC compared with the matched adjacent normal tissues. In addition, we examined the candidate miRNA expression in two groups of ADH blood samples: 28 sADHs and 32 cADHs by qRT-PCR. We found that miR-671-5p expression was decreased in cADHs, but not in sADHs, compared with their matched normal controls. Our recent publication demonstrated that miR-671-5p functions as a tumor suppressor miRNA during breast cancer progression by regulating FOXM1 expression. Using NanoString technology, we found another miRNA, miR-545-3p to be significantly overexpressed in cADHs compared with sADH. miR-545-3p is related to Snai2, which is a member of Snail family transcription factor, encoding a transcription repressor involving in epithelial-mesenchymal transitions (EMT). Our data suggest that miRNAs, such as miR-671-5p and miR-545-3p may be potential circulating biomarkers for early breast cancer detection following mammography and CNB

Continuum and line modeling of disks around young stars II. Line diagnostics for GASPS from the DENT grid

Aims. We want to understand the chemistry and physics of disks on the basis of a large unbiased and statistically relevant grid of disk models. One of the main goals is to explore the diagnostic power of various gas emission lines and line ratios for deriving main disk parameters such as the gas mass. Methods. We explore the results of the DENT grid (Disk Evolution with Neat Theory) that consists of 300 000 disk models with 11 free parameters. Through a statistical analysis, we search for correlations and trends in an effort to find tools for disk diagnostic. Results. All calculated quantities like species masses, temperatures, continuum and line fluxes differ by several orders of magnitude across the entire parameter space. The broad distribution of these quantities as a function of input parameters shows the limitation of using a prototype T Tauri or Herbig Ae/Be disk model. The statistical analysis of the DENT grid shows that CO gas is rarely the dominant carbon reservoir in disks. Models with large inner radii (10 times the dust condensation radius) and/or shallow surface density gradients lack massive gas phase water reservoirs. Also, 60% of the disks have gas temperatures averaged over the oxygen mass in the range between 15 and 70 K; the average gas temperatures for CO and O differ by less than a factor two. Studying the observational diagnostics, the [CII] 158 \mum fine structure line flux is very sensitive to the stellar UV flux and presence of a UV excess and it traces the outer disk radius (Rout). In the submm, the CO low J rotational lines also trace Rout. Low [OI] 63/145 line ratios (< a few) can be explained with cool atomic O gas in the uppermost surface layers leading to self-absorption in the 63 \mum line; this occurs mostly for massive non-flaring, settled disk models without UV excess. ... abbreviatedComment: 15 pages, 25 figures, accepted for publication in A&

Ultraviolet Spectroscopy of Asteroid (4) Vesta

We report a comprehensive review of the UV-visible spectrum and rotational lightcurve of Vesta combining new observations by Hubble Space Telescope and Swift Gamma-ray Burst Observatory with archival International Ultraviolet Explorer observations. The geometric albedos of Vesta from 220 nm to 953 nm are derived by carefully comparing these observations from various instruments at different times and observing geometries. Vesta has a rotationally averaged geometric albedo of 0.09 at 250 nm, 0.14 at 300 nm, 0.26 at 373 nm, 0.38 at 673 nm, and 0.30 at 950 nm. The linear spectral slope as measured between 240 and 320 nm in the ultraviolet displays a sharp minimum near a sub-Earth longitude of 20^{\circ}, and maximum in the eastern hemisphere. This is consistent with the longitudinal distribution of the spectral slope in the visible wavelength. The photometric uncertainty in the ultraviolet is ~20%, and in the visible wavelengths it is better than 10%. The amplitude of Vesta's rotational lightcurves is ~10% throughout the range of wavelengths we observed, but is smaller at 950 nm (~6%) near the 1-\mum band center. Contrary to earlier reports, we found no evidence for any difference between the phasing of the ultraviolet and visible/near-infrared lightcurves with respect to sub-Earth longitude. Vesta's average spectrum between 220 and 950 nm can well be described by measured reflectance spectra of fine particle howardite-like materials of basaltic achondrite meteorites. Combining this with the in-phase behavior of the ultraviolet, visible, and near-infrared lightcurves, and the spectral slopes with respect to the rotational phase, we conclude that there is no global ultraviolet/visible reversal on Vesta. Consequently, this implies a lack of global space weathering on Vesta, as previously inferred from visible-near-infrared data.Comment: 44 pages, 5 figures, 1 tabl

Cytosolic delivery of siRNA by ultra-high affinity dsRNA binding proteins

Abstract Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity. Despite concerns that excessively strong siRNA binding could prevent the discharge of siRNA from its carrier, higher affinity continually led to stronger silencing. We found that this improvement was due to both increased uptake of siRNA into the cell and improved pharmacodynamics inside the cell. Mathematical modeling predicted the existence of an affinity optimum that maximizes silencing, after which siRNA sequestration decreases potency. Our study characterizing the affinity dependence of silencing suggests that siRNA-carrier affinity can significantly affect the intracellular fate of siRNA and may serve as a handle for improving the efficiency of delivery. The two-agent delivery system presented here possesses notable biophysical properties and potency, and provide a platform for the cytosolic delivery of nucleic acids

The Complex Spin State of 103P-Hartley 2: Kinematics and Orientation in Space

We derive the spin state of the nucleus of Comet 103P/Hartley 2, its orientation in space, and its short-term temporal evolution from a mixture of observations taken from the DIXI (Deep Impact Extended Investigation) spacecraft and radar observations. The nucleus is found to spin in an excited long-axis mode (LAM) with its rotational angular momentum per unit mass, M, and rotational energy per unit mass, E, slowly decreasing while the degree of excitation in the spin increases through perihelion passage. M is directed toward (RA, Dec; J2000) = 8+/-+/- 4 deg., 54 +/- 1 deg. (obliquity = 48 +/- 1 deg.). This direction is likely changing, but the change is probably <6 deg. on the sky over the approx. 81.6 days of the DIXI encounter. The magnitudes of M and E at closest approach (JD 2455505.0831866 2011-11-04 13:59:47.310) are 30.0 +/- 0.2 sq. m/s and (1.56 +/- 0.02) X 10(exp -3) sq. m /sq. s respectively. The period of rotation about the instantaneous spin vector, which points in the direction (RA, Dec; J2000) = 300 +/- 3.2deg., 67 +/- 1.3 deg. at the time of closest approach, was 14.1 +/- 0.3 h. The instantaneous spin vector circulates around M, inclined at an average angle of 33.2 +/- 1.3 deg. with an average period of 18.40 +/- 0.13 h at the time of closest approach. The period of roll around the principal axis of minimum inertia (''long'' axis) at that time is 26.72 +/- 0.06 h. The long axis is inclined to M by approx. 81.2 +/- 0.6 deg. on average, slowly decreasing through encounter. We infer that there is a periodic nodding motion of the long axis with half the roll period, i.e., 13.36+/- 0.03 h, with amplitude of 1 again decreasing through encounter. The periodic variability in the circulation and roll rates during a cycle was at the 2% and 10-14% level respectively. During the encounter there was a secular lengthening of the circulation period of the long axis by 1.3 +/- 0.2 min/d, in agreement with ground-based estimates, while the period of roll around the long axis changed by approx. -4.4 min/d at perihelion. M decreased at a rate of 0.038 (sq m/s) per day in a roughly linear fashion. Assuming a bulk density between 230-300 kg/m3 and a total volume for the nucleus of 8.09 X 10(exp 8) cubic m, the net torque acting on the nucleus was in the range 0.8-1.1 X 10(exp 5) kg m(exp 2) /s(exp 2). In order to bring the spacecraft photometric and imaging data into alignment on the direction of M, the directions of the intermediate and short principal axes of inertia had to be adjusted by 33 deg (on the sky) from the values indicated by the shape model with an assumed homogeneous interior. The adjusted direction of the intermediate axis is RA, Dec = 302 deg., -16.5 deg.. The morning and evening terminators in the images are identified, and the variation of the insolation at three regions on the nucleus associated with active areas calculated. The plume of water vapor observed in the inner coma is found to be directed close to the direction of local gravity over the sub-solar region for a range of reasonable bulk densities. The plume does not follow the projected normal to the surface at the sub-solar point

Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping

Prolonged expression of the CRISPR-Cas9 nuclease and gRNA from viral vectors may cause off-target mutagenesis and immunogenicity. Thus, a transient delivery system is needed for therapeutic genome editing applications. Here, we develop an extracellular nanovesicle-based ribonucleoprotein delivery system named NanoMEDIC by utilizing two distinct homing mechanisms. Chemical induced dimerization recruits Cas9 protein into extracellular nanovesicles, and then a viral RNA packaging signal and two self-cleaving riboswitches tether and release sgRNA into nanovesicles. We demonstrate efficient genome editing in various hard-to-transfect cell types, including human induced pluripotent stem (iPS) cells, neurons, and myoblasts. NanoMEDIC also achieves over 90% exon skipping efficiencies in skeletal muscle cells derived from Duchenne muscular dystrophy (DMD) patient iPS cells. Finally, single intramuscular injection of NanoMEDIC induces permanent genomic exon skipping in a luciferase reporter mouse and in mdx mice, indicating its utility for in vivo genome editing therapy of DMD and beyond